US 20080220441A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0220441 A1 Birnbaum et al. (43) Pub. Date: Sep. 11, 2008

(54) ADVANCED DRUG DEVELOPMENT AND Related U.S. Application Data MANUFACTURING (63) Continuation-in-part of application No. 09/859,701, filed on May 16, 2001, Continuation-in-part of appli (76) Inventors: Eva R. Birnbaum, Los Alamos, cation No. 10/206,524, filed on Jul. 25, 2002, now NM (US); Andrew T. Koppisch, abandoned, Continuation-in-part of application No. Flagstaff, AZ (US); Sharon M. 10/621,825, filed on Jul. 16, 2003, now Pat. No. 6,858, Baldwin, Santa Fe, NM (US); 148. Benjamin P. Warner, Los Alamos, (60) Provisional application No. 60/850,594, filed on Oct. NM (US); T. Mark McCleskey, 10, 2006. Los Alamos, NM (US); Jeffrey Joseph Stewart, Los Alamos, NM Publication Classification (US); Jennifer A. Berger, Los (51) Int. C. Alamos, NM (US); Michael N. GOIN 33/53 (2006.01) Harris, Los Alamos, NM (US); GOIN 2L/76 (2006.01) Anthony K. Burrell, Los Alamos, GOIN 33/68 (2006.01) NM (US) GOIN 23/223 (2006.01) (52) U.S. Cl...... 435/7.1; 436/501; 436/172:436/86; Correspondence Address: 378/45 LOSALAMOS NATIONAL SECURITY, LLC (57) ABSTRACT LOS ALAMOS NATIONAL LABORATORY, PPO. BOX 1663, LC/IP, MS A187 X-ray fluorescence (XRF) spectrometry has been used for LOSALAMOS, NM 87545 (US) detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical, for estimating (21) Appl. No.: 11/974,156 the binding selectivity of a chemical versus chemical analogs, for measuring post-translational modifications of proteins, (22) Filed: Oct. 10, 2007 and for drug manufacturing. US 2008/0220441 A1 Sep. 11, 2008

ADVANCED DRUG DEVELOPMENT AND 0006. The chemical properties and in particular, the bind MANUFACTURING ing properties of a protein depend almost entirely on the exposed Surfaceamino acid residues of the polypeptide chain. RELATED APPLICATIONS These residues can form weak noncovalent bonds with other 0001. This application is a continuation-in-part of U.S. molecules. An effective binding between the protein, one patent application Ser. No. 09/859,701, now U.S. Patent example of a group of materials herein referred to as “recep Application 20030027129 entitled “Method for Detecting tors', and the material that binds to the receptor, referred to Binding Events. Using Micro-X-ray Fluorescence Spectrom herein as “chemical, generally requires that many weak etry,” which was published on Feb. 6, 2003, and a continua bonds form between the protein receptor and the chemical. tion-in-part of U.S. patent application Ser. No. 10/206,524, Chemicals include organic molecules, inorganic molecules, salts, metal ions, and the like. The bonds between the protein now U.S. Patent Application 2004.0017884 entitled “Flow and the chemical form at the “binding site' of the protein. The Method and Apparatus for Screening Chemicals. Using binding site is usually a cavity in the protein that is formed by Micro-X-Ray Fluorescence,” which was published on Jan. a specific arrangement of amino acids that often belong to 29, 2004, and a continuation-in-part of U.S. patent applica widely separated regions of the polypeptide chain and repre tion Ser. No. 10/621,825 filed Jul. 16, 2003, all hereby incor sent only a minor fraction of the total number of amino acids porated by reference herein. This application also claims the present in the chain. Chemicals should fit precisely into the benefit of U.S. Provisional Application Ser. No. 60/850,594 binding site for effective binding to occur. The shape of these filed Oct. 10, 2006, hereby incorporated by reference herein. binding sites can differ greatly among different proteins, and STATEMENT REGARDING FEDERAL RIGHTS even among different conformations of the same protein. Even slightly different conformations of the same protein 0002 This invention was made with government support may differ greatly in their binding abilities. For further dis under Contract No. DE-AC52-06NA25396 awarded by the cussion of the structure and function of proteins, see: Bruce U.S. Department of Energy. The government has certain Alberts et al., “Molecular Biology of the Cell', 2' edition, rights in the invention. Garland Publishing, Inc., New York, 1989; and H. Lodish et al., “Molecular Cell Biology', 4' edition, W. H. Freeman and FIELD OF THE INVENTION Company, 2000. 0003. The present invention relates generally to detecting 0007. After a receptor array is prepared, it is screened to binding events and more particularly to estimating binding determine which members have the desirable property or selectivities for chemicals, analogs, and drugs being tested properties. U.S. Pat. No. 5,143,854 to M. C. Pirrung et al. with receptors and then manufacturing those having a high entitled “Large Scale Photolithographic Solid Phase Synthe binding selectivity to the receptors. sis of Polypeptides and Receptor Binding Screening Thereof, which issued Sep. 1, 1992, hereby incorporated by reference, describes one Such screening method. A polypep BACKGROUND OF THE INVENTION tide array is exposed to a ligand (an example of a chemical) to 0004. The desire to hasten the identification of potentially determine which members of the array bind to the ligand. The important drugs, catalysts, chemical and biological sensors, ligands described are radioactive, or are "tagged', i.e. medical diagnostics, and other materials is a constant chal attached via one or more chemical bonds to a chemical por lenge that has prompted the use of combinatorial synthetic tion that fluoresces when exposed to non-ionizing, ultraviolet and Screening strategies for synthesizing these materials and radiation. Thus, the attached portion, i.e. the tag, makes the screening them for desirable properties. Combinatorial Syn chemical visible by interrogation with ultraviolet radiation. thesis involves assembling a “library’, i.e. a very large num Tagged molecules have also been used to aid in sequencing ber of chemically related compounds and mixtures, usually in immobilized polypeptides as described, for example, in U.S. the form of an array on a Substrate Surface. High throughput Pat. No. 5,902,723 to W. J. Dower et al. entitled “Analysis of screening of an array involves identifying which members of Surface Immobilized Polymers Utilizing Microfluorescence the array, if any, have the desirable property or properties. The Detection.” which issued May 11, 1999. Immobilized array form facilitates the identification of a particular material polypeptides are exposed to molecules labeled with fluores on the Substrate. Combinatorial arrays and high-throughput cent tags. The tagged molecules bind to the terminal mono screening techniques have been used to solve a variety of mer of a polypeptide, which is then cleaved and its identity problems related to the development of biological materials determined. The process is repeated to determine the com Such as proteins and DNA because the screening techniques plete sequence of the polypeptide. can be used to rapidly assay many biological materials. 0008. It is generally assumed that the attachment of a 0005. The binding properties of a protein largely depend fluorescent tag to a chemical only serves to make visible the on the exposed Surface amino acid residues of its polypeptide otherwise invisible chemical, and does not alter its binding chain (see, for example, Bruce Alberts et al., “Molecular properties. Since it is well known that even Small changes to Biology of the Cell", 2" edition, Garland Publishing, Inc., the structure of a molecule could affect its function, this New York, 1989; and H. Lodish et al., “Molecular Cell Biol assumption that a tagged chemical, i.e. a 'surrogate', has the ogy”, 4" edition, W. H. Freeman and Company, 2000). These same binding affinity as the untagged chemical may not be a amino acid residues can form weak noncovalent bonds with valid one. Small structural changes that accompany even a ions and molecules. Effective binding generally requires the conformational change of a receptor have been known to formation of many weak bonds at a “binding site, which is affect the binding affinity of the receptor. The tagged surro usually a cavity in the protein formed by a specific arrange gates are structurally different from their untagged counter ment of amino acids. There should be a precise fit with the parts, and these structural differences could affect their bind binding site for effective binding to occur. ing affinities. Since binding affinities derived using tagged US 2008/0220441 A1 Sep. 11, 2008

Surrogates are suspect, the binding properties of receptors and which are referred to herein as “analogs of the lead com chemicals should be evaluated using the untagged chemical pound, are synthesized and tested in order to determine which or receptor and not with a tagged Surrogate. of these chemicals, if any, exhibits an even higher binding 0009 Pharmaceutical chemicals are the active ingredients affinity. in drugs, and it is believed that their therapeutic properties are 0013 The preparation and high-throughput screening of linked to their ability to bind to one or more binding sites. The biological arrays is exemplified by the following papers: H. shapes of these binding sites may differ greatly among dif Zhu and M. Snyder, “Protein Chip Technology (Review). ferent proteins, and even among different conformations of Current Opinion in Chemical Biology, Vol. 7, pp. 55-63, the same protein. Even slightly different conformations of the (2003); G. MacBeath and S. L. Schreiber, “Printing Proteins same protein may differ greatly in their binding abilities. For As Microarrays For High-Throughput Function Determina these reasons, it is extremely difficult to predict which chemi tion.” Science, vol. 289, pp. 1760-1763, (2000); E.T. Funget cals will bind effectively to proteins. al., “Protein biochips for differential profiling.” Analytical 0010 Development and manufacturing for a new pharma Biotechnology, Vol. 12, pp. 65-69, (2001); T. Kukar et al., ceutical chemical for a drug, i.e. drug development, generally “Protein Microarrays to Detect Protein Protein Interactions involves determining the binding affinities between a poten Using Red and Green Fluorescent Proteins.” Analytical Bio tial pharmaceutical chemical (preferably a water soluble chemistry, vol. 306, pp. 50-54, (2002); G. Y. J. Chen et al., organic chemical that can dissolve into the blood stream) and “Developing a Strategy for Activity-Based Detection of a receptor (generally a biological material Such as an enzyme Enzymes in a Protein Microarray.” ChemBioChem, pp. 336 or non-enzyme protein, DNA, RNA, human cell, plant cell, 339, (2003); K. Martin et al., “Quantitative analysis of protein animal cell, and the like) at many stages of the drug develop phosphorylation status and protein kinase activity on ment process. The receptor may also be a microorganism (e.g. microarrays using a novel fluorescent phosphorylation sensor prion, virus, bacterium, spores, and the like) in whole or in dye.” Proteomics, Vol. 3, pp. 1244-1255, (2003); J. Burbaum part. The drug development process typically involves proce and G. M. Tobal, “Proteomics in drug discovery. Current dures for combining potential pharmaceutical chemicals with Opinion in Chemical Biology, Vol. 6, pp. 427-433. (2002); I. receptors, detecting chemical binding between the potential A. Hemmilä and P. Hurskainen, “Novel detection strategies pharmaceutical chemicals and the receptors and determining for drug discovery. Drug Discovery Today, Vol. 7, pp. S150 the binding affinity and kinetics of binding of a receptor to a S156, (2002), Pages S150-S156; all incorporated herein by chemical to form a complex or the kinetics of release of a reference. bound chemical from a complex. The binding affinity is 0014 Some screening methods are described in the fol defined herein as the associative equilibrium constant Ka for lowing patents, all of which are hereby incorporated by ref the following equilibrium expression: CCC. m(chemical)+receptor ASchemical-receptor 0015 U.S. Pat. No. 6,147,344 to D. Allen Annis et al. complex entitled “Method for Identifying Compounds in a Chemical Mixture', which issued Nov. 14, 2000, describes a method for 0011. The binding affinity, Ka, is defined by equation automatically analyzing mass spectrographic data from mix (1) below. tures of chemical compounds. Ka=chemical-receptor complex receptorchemi 0016 U.S. Pat. No. 6,344,334 to Jonathan A. Ellman et al. cal" (1) entitled “Pharmacophore Recombination for the Identifica In equation (1), chemical-receptor complex is the concen tion of Small Molecule Drug Lead Compounds,” which tration in moles per liter of the chemical-receptor complex, issued Feb. 5, 2002, describes a method for identifying a drug receptor is the concentration in moles per liter of the recep lead compound by contacting target biological molecules tor, m is the number of molecules of chemical that bind to with cross-linked binding fragments. each molecule of receptor, and chemical is the concentra (0017 U.S. Pat. No. 6,395,169 to Ole Hindsgaul et al. tion in moles per liter of the chemical. Any effects due to entitled "Apparatus for Screening Compound Libraries.” concentration can be simplified if the concentration of chemi which issued May 28, 2002, describes an apparatus that cal used were the same for all receptors. employs frontal chromatography combined with mass spec 0012 Nowadays, the drug development process may trometry to identify and rank members of a library that bind to involve the rapid screening of hundreds or thousands of a target receptor. chemicals in order to identify a “lead compound,” which is 0018. Other current high-throughput screening methods, one of the many tested that binds very strongly, i.e. has a high along with their associated drawbacks, are listed in TABLE 1 binding affinity, with a particular receptor. After Such a lead below, which is taken from the following paper. H. Zhu and compound has been identified, then other potential pharma M. Snyder, “Protein Chip Technology (Review). Current ceutical chemicals similar in structure to the lead compound, Opinion in Chemical Biology, Vol. 7, pp.55-63, (2003).

TABLE 1

Detection Technique Probe Labeling Data Acquirement ELISA (Enzyme-Linked Enzyme-Linked Antibodies CCD Imaging Immunosorbent Assay) Isotopic Labeling Radioisotope Labeled Analyte X-Ray Film Or Phospoimager Sandwich Immunoassay Fluorescently Labeled Laser Scanning Antibodies US 2008/0220441 A1 Sep. 11, 2008

TABLE 1-continued Detection Technique Probe Labeling Data Acquirement Surface Plasmon Resonance Receptor must be attached to Refractive Index Change a Surface Non-Contact Atomic Force None Surface Topological Change Microscopy Planar Waveguide Fluorescently Labeled CCD Imaging Antibodies SELDI (Surface Enhanced None Mass Spectrometry Laser Desorption Ionization Mass Spectrometry) Electrochemical Metal-Coupled Analyte Conductivity Measurement

0019 TABLE 1 shows that most of the listed screening method for identifying binding events between potential methods have the same drawback: they require either radio pharmaceutical chemicals and receptors (e.g. proteins). The labeled chemicals, chemicals that have been altered with a method involves modifying a mixture of potential pharma fluorescent tag, or chemicals that have been altered with a ceutical chemicals by adding at least one receptor to the metal tag. mixture. After allowing sufficient time for any bound com 0020 X-ray fluorescence (XRF) spectrometry is a power plex between any of the potential pharmaceutical chemicals ful spectroscopic technique that has been used to determine and any of the receptors to form, if such a complex can form, the elements that are present in a chemical sample, and to the resulting solution is flow separated into at least two com determine the quantity of those elements in the sample. The ponents. Each component is exposed to an X-ray excitation underlying physical principle of the method is that when an beam. If the exposed component emits a detectable X-ray atom of a particular element is irradiated with X-ray radia fluorescence signal, that component is isolated. The identity tion, the atom ejects a core electron Such as a Kshell electron. of any isolated component can be determined using one or The resulting atom is in then an excited State, and it can return more standard analytical techniques, such as gas chromatog to the ground State by replacing the ejected electron with an raphy, liquid chromatography, mass spectrometry, nuclear electron from a higher energy orbital. This is accompanied by magnetic resonance spectroscopy, infrared spectroscopy, the emission of a photon, i.e. X-ray fluorescence, and the photon energy is equal to the difference in the energies of the ultraviolet spectroscopy, visible spectroscopy, elemental two electrons. Each element has a characteristic set of orbital analysis, cell culturing, immunoassaying, and the like. energies and therefore, a characteristic X-ray fluorescence 0024. Effective drugs are selective drugs; they bind to a (XRF) spectrum. specific desired receptor, bypassing other receptors, to pro 0021. An XRF spectrometer is an apparatus capable of duce a desired therapeutic effect. This way, they target a irradiating a sample with an X-ray beam, detecting the X-ray specific disease in the body with minimal side effects; selec fluorescence from an element included in the sample, and tivity provides efficacy without undesirable side effects. using the X-ray fluorescence to determine which elements are 0025. The therapeutic index is a measure of drug selectiv present in the sample and providing the quantity of these ity that is ordinarily calculated from data obtained from elements. A typical, commercially available X-ray fluores experiments with animals. The therapeutic index of the drug cence spectrometer is the EDAX Eagle XPL energy disper is typically defined as the ratio of two numbers, LD50/ED50, sive X-ray fluorescence spectrometer, equipped with a micro where LD50 is the dose of a drug that is found to be lethal (i.e. focus X-ray tube, lithium drifted silicon solid-state detector, toxic) for 50 percent of the population of animals used for processing electronics, and Vendor Supplied operating soft testing the drug, and ED50 is the dose of the drug that is found ware. In principle, any element may be detected and quanti to have a therapeutic effect for 50 percent of that population. fied with XRF. More broadly, it is a measure of the how much of the drug is 0022 U.S. Patent Application 20030027129 entitled needed to produce a harmful effect relative to the amount “Method for Detecting Binding Events. Using Micro-X-ray needed to produce a beneficial effect. Theratio LD50/ED50 is Fluorescence Spectrometry, incorporated by reference therefore, a measure of the approximate “safety factor' for a herein, describes a method for detecting binding events using drug; a drug with a high therapeutic index can presumably be micro-X-ray fluorescence spectrometry. According to the administered with greater safety than one with a low index. 129 patent application, receptors are exposed to at least one 0026 Estimating the therapeutic index of a chemical potential chemical and arrayed on a substrate Support. Each involves measuring the binding affinity of a chemical to a first member of the array is exposed to X-ray radiation. The mag receptor, and measuring the binding affinity of the same nitude of a detectable X-ray fluorescence signal for at least one chemical to a second receptor. After measuring these binding element can be used to determine whether a binding event affinities, the ratio of the binding affinity of the chemical between a chemical and a receptor has occurred, and can divided by the amount of first receptor versus the binding provide information related to the extent of binding between affinity of the chemical divided by the amount of the second the chemical and receptor. receptor is determined. This ratio is provides an estimate of 0023 U.S. Patent Application 2004.0017884 entitled the “therapeutic index. For an example of using DNA arrays “Flow Method And Apparatus For Screening Chemicals with optical fluorescence high-throughput screening to esti Using Micro X-Ray Fluorescence,” which was published on mate a therapeutic index, see for example, R. Ulrich and S.H. Jan. 29, 2004, incorporated by reference herein, describes a Friend, “Toxicogenomics and Drug Discovery: Will New US 2008/0220441 A1 Sep. 11, 2008

Technologies Help Us Produce Better Drugs?’ Nature cence signal for a first heavy elementina first portion of a first Reviews Drug Discovery, v.1, pp. 84-88 (2002), incorporated receptor and in a first portion of a second receptor, the first herein by reference. heavy element being present in a chemical to be tested for 0027. There remains a need for simpler methods for mea binding to the receptors; establishing a baseline X-ray fluo Suring binding affinities and selectivities, estimating the rescence signal for a second heavy element in a second por therapeutic index of a chemical, and for expediting drug tion of the first receptor and in a second portion of a second manufacturing, receptor, the second heavy element being present in an analog 0028. Therefore, an object of the present invention is to of the chemical to be tested for binding to the receptors: provide a method for measuring binding affinities of chemi exposing the first portions of the receptors to the chemical and cals. allowing the chemical to bind to them to form a first chemical 0029. Another object of the present invention is to provide receptor complex and a second chemical-receptor complex; a method for measuring selectivity of chemicals binding to measuring the X-ray fluorescence signal due to the first heavy receptors. element present in the first chemical-receptor complex and in 0030 Yet another object of the invention is to provide a the second chemical-receptor complex; exposing the second method for estimating the therapeutic index of a chemical. portions of the receptors to the analog and allowing the analog 0031 Still another object of the invention is to provide a to bind to them to form a first analog-receptor complex and a method that employs X-ray fluorescence for drug manufac second analog-receptor complex; measuring the X-ray fluo ture. rescence signal due to the second heavy element present in the 0032. Additional objects, advantages and novel features of first analog-receptor complex and in the second analog-re the invention will be set forth in part in the description which ceptor complex; calculating the net X-ray fluorescence signal follows, and in part will become apparent to those skilled in due to the first heavy element in the first chemical-receptor the art upon examination of the following or may be learned complex by Subtracting the baseline X-ray fluorescence signal by practice of the invention. The objects and advantages of the of the first portion of the first receptor from the measured invention may be realized and attained by means of the instru X-ray fluorescence signal of the of the first chemical-receptor mentalities and combinations particularly pointed out in the complex; calculating the net X-ray fluorescence signal due to appended claims. the first heavy element present in the second chemical-recep tor complex by Subtracting the baseline X-ray fluorescence SUMMARY OF THE INVENTION signal of the first portion of the second receptor from the 0033. In accordance with the purposes of the present measured X-ray fluorescence signal of the second chemical invention, as embodied and broadly described herein, the receptor complex, calculating the net X-ray fluorescence sig present invention includes a method for estimating the bind nal due to the second heavy element in the first analog ing selectivity of a chemical having at least one heavy element receptor complex by Subtracting the baseline X-ray (i.e. an element having an atomic number of nine or higher) to fluorescence signal of the second portion of the first receptor at least two receptors. The method includes establishing a from the measured X-ray fluorescence signal of the of the first baseline X-ray fluorescence signal for a heavy element in a analog-receptor complex; calculating the net X-ray fluores portion of a first receptor and in a portion of at least one more cence signal due to the second heavy element present in the receptor that may be the same or different from the first second analog-receptor complex by Subtracting the baseline receptor, the heavy element being present in a chemical to be X-ray fluorescence signal of the second portion of the second tested for binding to the receptors; exposing the receptors to receptor from the measured X-ray fluorescence signal of the the chemical and allowing the chemical to bind to them to second analog-receptor complex; estimating the selectivity of form a first chemical-receptor complex and at least one more the chemical to binding to the receptors by dividing the net chemical-receptor complex; measuring the X-ray fluores X-ray fluorescence of the first chemical-receptor complex by cence signals due to the heavy element in the first chemical the amount of receptor in the first portion of the first receptor receptor complex and in the at least one more chemical to obtaina first quotient, dividing the net X-ray fluorescence of receptor complex; Subtracting the baseline X-ray fluorescence the second chemical-receptor complex by the amount of signal of the first receptor from the measured X-ray fluores receptor in the first portion of the second receptor to obtain a cence signal of the of the first chemical-receptor complex to second quotient; estimating the selectivity of the analog to obtain a first net X-ray fluorescence signal; Subtracting the binding to the receptors by dividing the net X-ray fluorescence baseline X-ray fluorescence signal of the at least one more of the first analog-receptor complex by the amount of receptor receptor from the measured X-ray fluorescence signal of the in the second portion of the first receptor to obtain a third of the at least one more chemical-receptor complex to obtain quotient, dividing the net X-ray fluorescence of the second at least one more net X-ray fluorescence signal; and then analog-receptor complex by the amount of receptor in the estimating the selectivity of the chemical by dividing the first second portion of the second receptor to obtain a fourth quo net X-ray fluorescence signal by the amount of receptor in the tient; and comparing first quotient to the second quotient to portion of the first receptor to obtain a first quotient, dividing the third quotient to the fourth quotient. the at least one more net X-ray fluorescence signal by the 0035. The invention also includes a method for manufac amount of receptor in the portion of the at least one more turing a drug. The method includes establishing a baseline receptor to obtain at least one more quotient, and then com X-ray fluorescence signal for a heavy element in a portion of paring the first quotient to the at least one more quotient. a first receptor and in a portion of at least one more receptor 0034. The invention also includes a method forestimating that may be the same or different from the first receptor, the the binding selectivity of a chemical versus at least one analog heavy element being present in a chemical to be tested for of the chemical to at least two receptors, the chemical and the binding to the receptors; exposing the receptors to the chemi at least one analog each having at least one heavy element. cal and allowing the chemical to bind to them to form a first The method includes establishing a baseline x-ray fluores chemical-receptor complex and at least one more chemical US 2008/0220441 A1 Sep. 11, 2008 receptor complex; measuring the X-ray fluorescence signals receptor complex by the amount of receptor in the first portion due to the heavy element in the first chemical-receptor com of the first receptor to obtain a first quotient, dividing the net plex and in the at least one more chemical-receptor complex; X-ray fluorescence of the second chemical-receptor complex Subtracting the baseline X-ray fluorescence signal of the first by the amount of receptor in the first portion of the second receptor from the measured X-ray fluorescence signal of the receptor to obtain a second quotient; estimating the selectivity of the first chemical-receptor complex to obtain a first net of the analog to binding to the receptors by dividing the net X-ray fluorescence signal; Subtracting the baseline X-ray fluo X-ray fluorescence of the first analog-receptor complex by the rescence signal of the at least one more receptor from the amount of receptor in the second portion of the first receptor measured X-ray fluorescence signal of the of the at least one to obtain a third quotient, dividing the net X-ray fluorescence more chemical-receptor complex to obtain at least one more of the second analog-receptor complex by the amount of net X-ray fluorescence signal; estimating the selectivity of the receptor in the second portion of the second receptor to obtain chemical by dividing the first net X-ray fluorescence signal by a fourth quotient; and comparing first, second, third, and the amount of receptor in the portion of the first receptor to fourth quotients to determine if the chemical or analog is the obtain a first quotient, dividing the at least one more net X-ray more selective and manufacturing the more selective one in fluorescence signal by the amount of receptor in the portion of Sufficient quantity for use as a drug. the at least one more receptor to obtain at least one more 0037. The invention also includes a method for comparing quotient, and then comparing the first quotient to the at least the ability of at least one chemical in a first solution to bind to one more quotient; and manufacturing the chemical in Suffi a portion of at least one receptor versus the ability of that cient quantity for use as a drug if the first quotient and the at chemical in a second solution to bind to a separate portion of least one more quotient are different by at least one percent. the same at least one receptor. The method includes establish 0036. The invention also includes a method for manufac ing a baseline X-ray fluorescence signal for a heavy element turing a drug. The method includes establishing a baseline in a first portion of a receptor and for the heavy element in a X-ray fluorescence signal for a first heavy element in a first separate portion of the receptor, the heavy element being portion of a first receptor and in a first portion of a second present in a chemical that is being tested for binding to the receptor, the first heavy element being present in a chemical receptor, exposing the first portion of the receptor to a first to be tested for binding to the receptors; establishing a base Solution that includes the chemical, and allowing the chemi line X-ray fluorescence signal for a second heavy element in cal to bind to the receptor to form a first chemical-receptor a second portion of the first receptor and in a second portion complex; exposing the separate portion of the receptor to a of a second receptor, the second heavy element being present second solution also includes the chemical, and allowing the in an analog of the chemical to be tested for binding to the chemical to bind to the receptor to form a second chemical receptors; exposing the first portions of the receptors to the receptor complex; measuring the X-ray fluorescence signals chemical and allowing the chemical to bind to them to form a due to the heavy element in the first chemical-receptor com first chemical-receptor complex and a second chemical-re plex and in the second chemical-receptor complex; calculat ceptor complex; measuring the X-ray fluorescence signal due ing the net X-ray fluorescence signal due to the heavy element to the first heavy element present in the first chemical-recep in the first chemical-receptor complex by Subtracting the tor complex and in the second chemical-receptor complex; baseline X-ray fluorescence signal of the first portion of recep exposing the second portions of the receptors to the analog tor from the measured X-ray fluorescence signal of the first and allowing the analog to bind to them to form a first analog chemical-receptor complex; calculating the net X-ray fluores receptor complex and a second analog-receptor complex; cence signal due to the heavy element in the second chemical measuring the X-ray fluorescence signal due to the second receptor complex by Subtracting the baseline X-ray fluores heavy element present in the first analog-receptor complex cence signal of the separate portion of receptor from the and in the second analog-receptor complex; calculating the measured X-ray fluorescence signal of the second chemical net X-ray fluorescence signal due to the first heavy element in receptor complex; and estimating the binding selectivity of the first chemical-receptor complex by Subtracting the base the chemical in the first solution versus the second solution by line x-ray fluorescence signal of the first portion of the first dividing the net X-ray fluorescence signal of the first chemi receptor from the measured X-ray fluorescence signal of the cal-receptor complex by the amount of receptor in the first of the first chemical-receptor complex; calculating the net portion of the receptor to obtain a first quotient, dividing the X-ray fluorescence signal due to the first heavy element net X-ray fluorescence of the second chemical-receptor com present in the second chemical-receptor complex by Subtract plex by the amount of receptor in the separate portion of the ing the baseline X-ray fluorescence signal of the first portion receptor to obtain a second quotient, and then comparing the of the second receptor from the measured X-ray fluorescence first quotient to the second quotient. signal of the second chemical-receptor complex; calculating 0038. The invention also includes a method forestimating the net X-ray fluorescence signal due to the second heavy the relative effectiveness of at least two drugs, each drug element in the first analog-receptor complex by Subtracting having at least one heavy element. The method includes pro the baseline X-ray fluorescence signal of the second portion of viding a sample from a medical patient, the sample compris the first receptor from the measured X-ray fluorescence signal ing at least a first portion and a second portion of a first of the of the first analog-receptor complex, calculating the net receptor and a first portion and a second portion of a second X-ray fluorescence signal due to the second heavy element receptor; establishing a baseline X-ray fluorescence signal for present in the second analog-receptor complex by Subtracting a first heavy element in the first portion of the first receptor the baseline X-ray fluorescence signal of the second portion of and in the first portion of the second receptor, the first heavy the second receptor from the measured X-ray fluorescence element being present in a first drug to be tested for binding to signal of the second analog-receptor complex; estimating the the first and second receptors; establishing a baseline X-ray selectivity of the chemical to binding to the receptors by fluorescence signal for a second heavy element in the second dividing the net X-ray fluorescence of the first chemical portion of the first receptor and in the second portion of the US 2008/0220441 A1 Sep. 11, 2008

second receptor, the second heavy element being present in a excited state of the heavy element, the excited state of the second drug to be tested for binding to first and second recep heavy element having a fluorescence lifetime that is less than tors; exposing the first portion of the first receptor and the first the dead time of the X-ray detector, calculating the net X-ray portion of the second receptor to the first drug and allowing fluorescence signal due to the heavy element in the chemical the drug to bind to the first receptor to form a first drug receptor complex by Subtracting the baseline X-ray fluores receptor complex, and to bind to the second receptor to form cence signal of the portion of receptor from the measured a second drug-receptor complex; measuring the X-ray fluo X-ray fluorescence signal of the chemical-receptor complex; rescence signal due to the first heavy element present in the and estimating the binding affinity of the chemical for the first drug-receptor complex and in the second drug-receptor receptor by dividing the net X-ray fluorescence signal of the complex; exposing the second portion of the first receptor and chemical-receptor complex by the amount of the receptor in the second portion of the second receptor to the second drug the portion of the receptor. and allowing the second drug to bind to the first receptor to 0040. The invention also includes a method for detecting form a third drug-receptor complex, and to bind to the second protein modification. The method includes establishing a receptor to form a fourth drug-receptor complex; measuring baseline X-ray fluorescence signal for a heavy element in a the X-ray fluorescence signal due to the second heavy element portion of a protein; exposing the portion of protein to con present in the third drug-receptor complex and in the fourth ditions that may alter the amount of the heavy element present drug-receptor complex; calculating a first net X-ray fluores in the portion of the protein and then measuring the X-ray cence signal due to the first heavy element present in the first fluorescence signal due to the heavy element; and Subtracting drug-receptor complex by Subtracting the baseline X-ray fluo the baseline X-ray fluorescence signal from the measured rescence signal of the first portion of the first receptor from X-ray fluorescence signal. the measured x-ray fluorescence signal of the of the first drug-receptor complex; calculating a second net X-ray fluo DETAILED DESCRIPTION rescence signal due to the first heavy element present in the second drug-receptor complex by Subtracting the baseline Overview X-ray fluorescence signal of the first portion of the second 0041. The present invention consists of improvements to receptor from the measured X-ray fluorescence signal of the the invention described in published US Patent Application second drug-receptor complex; calculating a third net X-ray 20040235059 “Drug Development and Manufacturing to fluorescence signal due to the second heavy element in the Benjamin P. Warner, T. Mark McCleskey, and Anthony K. third drug-receptor complex by Subtracting the baseline X-ray Burrell, filed Jun. 29, 2004. These improvements consist of fluorescence signal of the second portion of the first receptor the following additional steps to be used in the process that from the measured x-ray fluorescence signal of the of the third improve the signal or signal to noise ratios obtained from the drug-receptor complex; calculating a fourth net X-ray fluo measurement, and specific requirements for preparation of rescence signal due to the second heavy element present in the samples that provide improved signals or signal to noise fourth drug-receptor complex by Subtracting the baseline ratios. All of these methods may be used with multiple X-ray fluorescence signal of the second portion of the second samples to provide comparisons between samples, or with receptor from the measured X-ray fluorescence signal of the single samples to obtain information about the sample. fourth drug-receptor complex; calculating binding quotients for the first drug by dividing the first net X-ray fluorescence Substrates signal by the amount of receptor in the first portion of the first 0042. A key improvement to US Patent Application receptor to obtain a first quotient, dividing the second net 20040235059 is the use of sample substrates which minimize X-ray fluorescence signal by the amount of receptor in the first noise. Characteristics to be optimized include the thickness of portion of the second receptor to obtain a second quotient; the substrate; the chemical and elemental composition of the calculating binding quotients for the second drug by dividing substrate; and the variability in the chemical composition of the third net X-ray fluorescence signal by the amount of recep the surface of the substrate. tor in the second portion of the first receptor to obtain a third 0043. Substrates are preferably thin enough to minimize quotient, dividing the fourth net X-ray fluorescence signal by the scattering of incident X-rays. Thick Substrates cause scat the amount of receptor in the second portion of the second tering in the X-ray portion of the electromagnetic spectrum. receptor to obtain a fourth quotient; and comparing the first, Preferably, the substrates are less than 500 microns thick, and second, third, and fourth quotients to estimate the relative more preferably the substrates are less than about 50 microns effectiveness of the first drug versus the second drug. thick. Most preferably, the substrates are between twenty (20) 0039. The invention also includes a method forestimating nanometers thick and twenty-five (25) microns thick. binding affinity. The method involves depositing a portion of Examples of materials which may be conveniently used a receptor on a Substrate; establishing a baseline X-ray fluo include 0.02 micron thick, 99.99% pure gold foil, available rescence signal for a heavy element in the portion of the from Lebow Company, 5960 Mandarin Ave., Goleta, Calif. receptor, the heavy element being present in a chemical being 93.117 U.S.A.: 0.07 micron thick, 99.95% pure aluminum testing for binding to the receptor, exposing the receptor to a foil, available from Lebow Company, 5960 Mandarin Ave., Solution comprising the chemical at a first temperature, and Goleta, Calif. 93117 U.S.A.: 0.1 micron through 20 micron allowing the chemical to bind to the receptor to form a chemi thick PARYLENE NR), available from Lebow Company, cal-receptor complex; measuring the X-ray fluorescence sig 5960 Mandarin Ave., Goleta, Calif. 93117 U.S.A.; and 0.5 nal due to the heavy element in the chemical-receptor com micron thick to 25.0 micron thick, 99.99% pure titanium foil, plex using excitation photons having an energy of at least 300 available from Lebow Company, 5960 Mandarin Ave., electron-volts to electronically excite the heavy element, and Goleta, Calif. 93117 U.S.A.; and 4 micron thick to 8 micron detecting emission photons using an X-ray detector having a thick polypropylene, available from Lebow Company, 5960 dead time, the emission photons being generated from an Mandarin Ave., Goleta, Calif. 93117 U.S.A. Other substrates US 2008/0220441 A1 Sep. 11, 2008 that are conveniently used are AP1, AP3, ProLINE Series 10, element to be measured in the sample. In this paragraph, ProLINE Series 20. DuraBeryllium substrates from Moxtek, substantially free is defined as a substrate which produces less 452 West 1260 North, Orem, Utah 84057. Other substrates than 10% of the signal produced by the sample, which when that are conveniently used are Ultralene R, Mylar, polycar measured using the same X-ray fluorescence conditions. bonate, Prolene, and Kapton, available from SPEX CertiPrep Ltd, 2 Dalston Gardens, Stanmore, Middx HA7 1BQ, Substrates: Focusing Chips ENGLAND. Other substrates that may be conveniently used 0045. The invention also consists of preparing a protein are Hostaphan(R), polyester, and Etnom R available from sample on a focusing chip. Focusing chips typically consist of Chemplex Industries, Inc., 2820 SW 42nd Avenue, Palm City, a Substrate having a pattern of hydrophobic and hydrophilic Fla. 34990-5573 USA. The substrate is preferably a polymer, regions. Preferably, each hydrophilic region is circumscribed and more preferably is a polymer that contains carbon. Radia by a hydrophobic region. When a sample of an aqueous tion produced by radioactive materials will produce noise in Solution is placed on a hydrophilic region of the chip, the the measurement. The substrate is preferably substantially Surrounding hydrophobic region repels the solvent and free of the elements technetium, thorium, and uranium. Most causes the sample to dry preferentially over the hydrophilic of the chemicals to be studied using the present invention will region. The drying may be accomplished through any means, contain one or more of the following elements: oxygen, fluo including simple ambient air drying or heating. In this way, rine, phosphorus, sulfur, and chlorine. Therefore, to minimize larger droplet may be dried into a predefined region using a unwanted signal from these elements in the focusing chip, the focusing chip instead of a non-focusing slide. Focusing chips focusing chip should consist of less than 50% by mass of at have been developed for depositing proteins for Matrix least one of these elements (fluorine, oxygen, phosphorus, Assisted Laser Desorption Ionization Mass Spectrometry sulfur, and chlorine). The substrate preferably comprises less (MALDI-MS). Some of these focusing chips were described than about 50% of at least one of the elements selected from at the 54th ASMS Conference on Mass Spectrometry, May the group comprising oxygen, fluorine, phosphorus, sulfur, 28-Jun. 1, 2006, Washington State Convention & Trade Cen and chlorine. Based on their structural and spectroscopic ter, Seattle, Wash., described on the internet at: http://www. properties, elements that are useful in the window include asms.org/Desktopmodules/inmergeabstractsearch/program beryllium, carbon, silicon, aluminum, iron, cobalt, and gold. printView.aspx?sess=WP13, and quoted below in the bulleted The substrate therefore preferably contains at least 10% of at list: least one of the following elements: beryllium, carbon, sili 0046) “Applications of a SAM-IMAC Biochip for the con, aluminum, iron, cobalt, and gold. The substrate prefer Purification and Concentration of Bioengineered or ably comprises greater than about 10% of at least one of the Phosphorylated Proteins with Detection by MALDI elements selected from the group comprising beryllium, car MS” by Christopher M. Belisle: Irene Y. Chen; Julie K. bon, silicon, aluminum, iron, cobalt, and gold. Mirshad: Udo Roth; Kerstin Steinert; and John A. 0044) Substrates may absorb scattered x-rays that may Walker, II; who stated that: “Immobilized metal affinity contribute to noise in the measurement. Substrates that absorb chromatography (IMAC) is a powerful technique which Scattered X-rays preferably have an X-ray emission peak is routinely used in the purification of biomolecules between about 2.984 KeV (e.g. silver) and about 6.947 KeV. containing a hexa-histidine tag, as well as phosphory (e.g. erbium) to avoid overlap with signals of interest. X-ray lated peptides/proteins. This wide range of affinities is emission peaks that are at higher energies than about 6.947 afforded by the chelation of specific metal ions by an KeV are generally non-productive for exciting the sample if it immobilized poly-valent ligand (i.e. IDA-Ni(II) for contains sulfur, phosphorus, or chlorine; although in cases hexa-His tags and IDA-Fe(III) for phosphorylated spe where the sample contains elements such as selenium, x-rays cies). The utility of IMAC surfaces formed from SAMs of higher energy may be useful. X-ray emission peaks from has been demonstrated with SPR. In this work, chelated the substrate that have energies between about 1.978 KeV metals allows for high affinity capture and optimal ori (e.g. iridium) and about 2.984 KeV (e.g. silver) are generally entation of tagged proteins for subsequent protein/pro counter-productive if the sample contains sulfur, chlorine, or tein interaction studies. We have developed a SAM phosphorus; this is the typical case for biological or pharma based biochip that takes full advantage of these ceutically-important samples. If the sample to be measured properties and allows for volume containment, sample contains phosphorus, then the substrate should not contain concentration and direct interface to and detection by Zirconium, phosphorus, platinum, gold, niobium, mercury, or MALDI-MS. Three distinct SAM regions were pat thallium. If the sample to be measured contains sulfur, then terned on a gold-coated biochip in a 96 well format. the substrate should not contain thallium, molybdenum, sul Each site was comprised of a circular capture Zone con fur, lead, bismuth, technetium, or ruthenium. If the sample to taining either NTA-Ni(II) or NTA-Fe(III) chemistry. be measured contains chlorine, then the substrate should not Each site is surrounded by a non-wettable, protein-re contain technetium, ruthenium, chlorine, rhodium, or palla sistant SAM region and is capable of retaining sample dium. X-ray emission peaks from substrates that are less than Volumes in excess of 25ul. Centered in the capture Zone 1.978 KeV are believed to be unproductive for exciting bio was a 0.6 mm analysis Zone consisting of a protein logical samples. The substrate should be substantially free of resistant SAM. After chelating the metal, samples con the elements that are not intended to be measured in the taining either His tags or phosphorylated amino acid sample if energy dispersive X-ray fluorescence (EDXRF) is to residues were applied and purified on-chip. Subsequent be used for analysis. Wavelength dispersive X-ray fluores release, concentration and detection of the captured ana cence (WDXRF) have been shown to differentiate different lytes was facilitated by focusing and the addition of chemical forms of elements, such as the sulfur compounds matrix.” Sulfate and sulfite; if WDXRF is used, then the substrate 0047 “Effects of Nanoporous Silica Thin Film Param should be substantially free of the same chemical form of the eters on LDI-MS Performance” by Srinivas Iyer, Raea US 2008/0220441 A1 Sep. 11, 2008

Hicks; Steven Madrid; and Andrew Dattelbaum; who dling, contamination and loss. At the routine sensitivity Stated that “The use of MALDI-TOF MS in Small mol level of mass spectrometry, monolayer Surface chemis ecule analysis has been limited due to matrix interfer try does not provide enough interaction sites for real ence. We have shown that ordered nanoporous silica thin world analysis. Subsequently we decided to use mono films on silicon substrates allow for the analysis of small lithic polymer chemistry that we had previously devel organic molecules without the addition of a matrix. Pat oped for capillary columns dedicated to proteomics terned nanoporous films are prepared by an evaporation applications and that affords 1 micron-thick film. Meth self-assembly method, followed by selective UV expo acrylate-based monoliths were anchored on a gold Sur Sure, to prepare Surfaces that may be spotted with many face using a linker bearing at its two extremities a dis different analytes. The patterned films have been shown ulfide moiety and a methacrylate group respectively, and to remain active for over a year under atmospheric con polymerisation was done according to an original living ditions. Here we report the effect of several variables, method. Non reactive and hydrophobic butylmethacry including film thickness, film porosity, instrumental set late (BMA) or reactive glycidylmethacrylate (GMA) tings and spotting technique, to optimize the mass spec may be used and mixed together in any proportions. analysis of Small peptides and other biomolecular Either silicon wafer coated with gold or low-cost printed samples on nanoporous silica thin films. Mesoporous board circuit coated with copper or gold may be used as thin films are made by withdrawing an oZonated silicon the starting Surface. Using printed board enables rapid crystal at a steady rate from a solution of TEOS, water, prototyping of patterned surfaces. Most of the experi ethanol, HCl, and templating Surfactant, then UV-pat ments described were done either on plain gold Surface terning the film to remove the template and expose ana or 400 um gold spots. We first tested the desalting effi lyte-absorbing pores. Film thickness and pore size can ciency using a laurylmethacrylate phase. One microliter be controlled by withdrawal speed and choice of surfac droplets of a salted (20%) solution containing various tant, respectively. These films are mounted directly onto peptides (1 picomolar) were placed on the Surface, and a standard MALDI plate. Fims of varying thickness and interactions were forced by several aspiration/ejection pore size were examined. Spotting conditions were also cycles. Spots were washed with water, extracted with examined using a solution of FITC labeled angiotensin. acetonitrile/water and analyzed offline either by ESI or Before MS, the spots were examined by fluorescent MALDI. In both cases, no adducts were detected on the microscopy to determine spot spreading and coverage. mass spectra. The second test involved a functionalized MS analysis was conducted on a Voyager DE-STR in glycidylmethacrylate on which was first linked trypsin. positive ion, reflector mode. Our data indicates that these After washing of the surface, one microliter of Cyto films require no special storage conditions to remain chrom C (1 picomolar) was deposited and let on the stable for over a year. Preliminary studies show that surface for a quarter of an hour. More water was added mesoporous silica thin films yield acceptable results in and the sample desalted. Resulting mass spectra showed terms of intensity and resolution for Small molecules a clean digestion, affording a high score identification on such as peptides and C60 and its derivatives. Reliable proteomics search engine. Analysis on crude biological data was obtained for acid hydrolysates of bacterial sid samples like human plasma will be also presented. The erophores. Optimizing spotting methods improved sig different parameters, monolith porosity and thickness, nal intensity by two orders of magnitude while retaining nature of monomers, droplet handling, are currently resolution. Fluorescence microscopy data shows that under investigation. We are also testing other monolithic spotting Small amounts of analyte, followed by remov phases we also developed for nano-LC capillary column ing excess Solution after a minute gives a uniform spread for phosphopeptide (IMAC) and glycopeptide (phenyl of sample, this is further substantiated by MS data. With boronic acid) isolation.” peptides and Small molecules, we observe that thinner 0049) “The Use of Reactive Surfaces for On-Chip films perform better. Small changes in pore size do not Immobilization of Biomolecules and Subsequent Puri appear to affect desorption-ionization significantly. fication/Concentration of Analytes for MALDI-MS. by However, when compared with MALDI, higher laser Julie K Mirshad; Christopher M Belisle; Irene Y Chen: fluences are needed with these thin films. Future work Udo Roth; Kerstin Steinert; and John A Walker II who will be directed towards improving sensitivity of this stated that Currently in proteomics there is an increasing approach.” demand for high affinity purification of small amounts of 0048 “Functionalized monolithic surfaces for single analytes from complex samples. This requires methods droplet sample handling by Mohammed Kaijout; Xiay that minimize sample handling and analyte loss while ang Wang: Christian Rolando: Séverine Le Gac; who being amenable to high-throughput processing. Typi stated that “We describe here functionalized monolithic cally, highly selective purifications have been achieved Surfaces for single droplethandling. In many cases mass by immobilized biomolecules such as mAb, steptavidin/ spectrometry analysts must face to single droplet han biotin or nucleic acids. The most frequently used chem dling either as the initial sample input of the analysis or istry reported in literature for such immobilizations are for sample preparation before nano-ESI or MALDI. The active esters (i.e. N-Hydroxysuccinimide NHS). We conventional strategy consists of dissolving the droplet have developed a novel biochip platform used in in more solvent so as to perform sample preparation on MALDI-MS that consists of multiple sites with differing devices working with continuous liquid flow. At the final Zones of wettability which enable immobilization of stage liquid must be concentrated to go back to a the these biomolecules with Subsequent concentration of droplet state. Therefore the development of surface the captured analytes. Three distinct SAM regions were chemistry for the purification of single liquid droplets patterned on a gold-coated biochip in a 96 well format. has a strong interest in order to minimize sample han Each site was comprised of a circular capture Zone con US 2008/0220441 A1 Sep. 11, 2008

taining the active NHS chemistry. These sites are 0.57(0.08) for a thin sample. The homogeneity of the capable of retaining sample Volumes in excess of 25ul sample preparation method was demonstrated for phos and are surrounded by a non-wettable, protein-resistant pholipids samples and crude lipid extracts. It was pos background SAM region. Centered in the capture Zone sible to separate groups of mouse serum based on their was a 0.6 mm analysis Zone consisting of a highly wet lipid spectra.” table, protein-resistant SAM that facilitates MALDI per 0051) “MALDI on Silicon' by Jae-Kuk Kim; and Ker formance. After protein immobilization, samples con mit K. Murray who stated that Porous silicon substrates taining complementary antigens in complex mixtures have been used in the past for Small molecule analyses were applied and purified on-chip. Subsequent release, with the matrix-free soft ionization method known as concentration and detection of the captured analytes desorption/ionization on silicon (DIOS). Non-porous were facilitated by focusing and the addition of matrix. silicon targets have been used with infrared lasers for In initial experiments, analytes were used in spike/re ionization that is similar DIOS in that a matrix is not covery experiments with various protein digests to test for specificity and the limits of detection (LOD) for the required and ionization occurs without interference biochip. In Subsequent experiments, mAb were immo from low mass background ions. In this study, we dem bilized and proteins were purified on-chip and then onstrate the benefits of using untreated silicon targets for digested in situ with trypsin. Sample clean-up was per matrix-assisted laser desorption ionization (MALDI). formed by either transferring to a reverse-phase 3 Zone Samples and matrix are deposited along with matrix on biochip or by SPE. Results comparing the advantages of a silicon wafer and were irradiated with a UV laser. The this technique are discussed resulting ions are mass separated in a time-of-flight mass 0050 “Enhanced MALDI ionization efficiency at the spectrometer. Riboflavin (MW: 376.4 Da, Formula: metal-matrix interface: practical and mechanistic con CHNO), bovine serum albumin (BSA, MW: sequences of samplethickness and preparation method.” 66,430.3 Da), lyophilized Escherichia coli strain W by Gregor McCombie; and Richard Knochenmuss, who (ATCC 9637), and phosphorylase b from rabbit muscle stated that "Electrosprayed spots of varying thickness (MW: 97 kDa) were ionized by MALDI on both non were evaluated for use as homogenous, high efficiency porous silicon Substrate and stainless steel Substrate. The MALDI samples. The layer at the metal/matrix interface dried droplet method was used to sample preparation for was found to give exceptionally strong signals. Ion both substrates. The Bruker Omniflex mass spectrom yields and intensity ratios can be understood in the con eter can be operated in linear and reflectron mode and text of the previously described quantitative MALDI uses a 337 nm nitrogen laser (Pulse width: 3 ns, Pulse model including the matrix-metal interfacial ionization energy: 200 LJ max.) at a repetition rate of 2 Hz for potential reduction effect (Knochenmuss, R. Anal. ionization. An accelerating Voltage of 19 kV was Chem. 2004, 76,3179-3184). The absolute and relative employed with delayed ion extraction. The typical het stabilities of ion signals were found to be at least a factor erogeneous MALDI sample deposit requires searching of 2 better for the thin electrosprayed spots, compared to for “sweet spot” to obtain the optimum mass spectrum spots prepared by dried droplet methods. The sample with a stainless steel substrate. One of the greatest preparation method was used for the analysis of yeast advantages of the untreated silicon Substrate is that it lipid composition. In order to detect differences in lipid leads to a homogeneous sample spot so that a search for content a stable sample preparation is necessary. Experi a Sweet spot is not necessary. Comparison of Small mol ments were performed on a commercial MALDITOF ecule LDI analysis of riboflavin showed significant dif instrument (Voyager DE STR, Applied Biosystems ference between silicon and stainless steel substrates. Framingham, Mass.). The mass range was from m/Z 100 The stainless steel target gave Small analyte peaks only to 1500. The electrospary sample deposition was done at high laser energy that also produced extensive back on a home built electrospray device using a CTC Pal ground due to ablation of material on the metal target. In autosampler for the sample injection. The spray Voltage contrast, the untreated silicon Substrate showed intense was 5 kV and the distance of the needle to the sample analyte peaks without background noise even at full plate 6 mm. Lipid extracts from yeast were done using laser energy. It was difficult to obtain signal from the the Bligh and Dyer method. Electrospary deposition of stainless steel target, but highly reproducible mass spec matrix (DHB) and analyte (Substance P or reserpine) on tra could be obtained for non-porous silicon substrate. a MALDI target plate of varying spray times allowed us BSA, Escherichia coli and phosphorylase b MALDI to control the thickness of the sample. Spray times mass spectra could also be obtained easily on the silicon between 2 and 30 seconds were used to demonstrate that substrate with high spot-to-spot reproducibility. The the MALDI ion yield is 10 to 100 times higher at the silicon target required somewhat higher threshold metal/matrix interface. The results were consistent with, energy compared to the metal target, but showed some and could be explained by a previously described what better signal-to-noise ratio and resolution than MALDI ionization model (Knochenmuss, R. Anal. stainless steel substrate for small molecule as well as Chem. 2004, 76, 3179-3184). The formation of more high molecule analyses. A Surface characteristic of non primary matrix ions was demonstrated by quantifying porous silicon Substrate is hydrophobic which makes a the suppression of the matrix signals (MSE score; Smaller and more concentrated sample spot after solvent McCombie, G. Knochenmuss, R. Anal. Chem. 2004, evaporation. It is possible that this produces homoge 76, 4990-4997) and comparing a thin versus a thick neous analyte and matrix crystals and efficiention for sample. While the MSI score for the thick sample was mation. An alternate explanation is that the lower num 0.94(0.06)—which is almost complete matrix suppres ber of electrons produced by irradiation of the silicon sion—the same conditions only gave a MSE score of results in less charge recombination and therefore US 2008/0220441 A1 Sep. 11, 2008

greater signal. Different target materials and Surface show any change in signal intensity and further investi imaging techniques are being used to explore ion forma gations are ongoing with older samples. These results tion from silicon targets.” Suggest that porous alumina on glass can be a potential 0.052 “Matrix-free Laser Desorption Ionization Mass matrix-less approach for LDI-MS proteomic analysis.” Spectrometry using Porous Alumina Thin Film Struc 0.053 An statistical analysis of factors related to ion tures.” by Ranu Nayak; and Daniel R Knapp who stated suppression in MALDI-TOF mass spectrometry” by that “Matrix-assisted laser desorption ionization Dongmei Yang; Michael S. Wisz: Kevin Ramkissoon; (MALDI) mass spectrometry (MS) has been established Morgan C. Giddings who stated that “Protein identifi as one of the key methods for proteomic analysis. cation relies heavily on the measurement of peptides by MALDI is complicated by the need to have good co a mass spectrometer, yet ion Suppression impedes pep crystallization of sample and matrix. Matrix-free meth tide measurement by causing a differential in their spec ods of laser desorption ionization (LDI) offer the poten tral intensities that can result in some peptide peaks tial to eliminate this complication. MS from porous being undetectable. The differing chemical properties of alumina Surfaces has been reported (R1-Anal. Chem. peptides are thought responsible for this phenomenon. 77, 5364-69, 2005), however, few details were provided We examined the correlations between observed peptide and the report did not describe a systematic study of the intensities and their amino acid sequence content for experimental parameters. We report here the LDI MS MALDI-TOF spectra in order to provide a predictive analysis of some peptides using anodized aluminum measure for the likelihood that a given peptide might be (Al) Surface on glass Substrates and an investigation of observed, given its sequence. These statistics may be the experimental factors controlling the MS signal inten used as an additional measure that can be factored into sity. Al thin films were grown on cleaned Pyrex glass the search engines to increase the accuracy of protein Substrates using athermal evaporation technique. The as identification, particularly for peptide mass fingerprint grown films were Subjected to anodization using a dc (PMF) data. We obtained TOF spectra on an ABI 4700 regulated power supply at 50V, 60V, and 90V in a 10 vol. mass spectrometer, corresponding to trypsin-digested % phosphoric acid solution (at room temperature). The spots taken from coumassie stained gels of E. coli cyto resulting porous oxide layer was confirmed by scanning solic extract. Proteins were identified by PMF analysis electron microscopy. The anodized samples were coated using Mascot and GFS searching tools, resulting in 350 with gold film by magnetron sputtering. Subsequently, matched proteins with significance p-0.05. We also gen different peptides (mass range-500 to 10,000 Da; con erated 30,000 control spectra by picking random sets of centration-0.1 to 1.0 mg/ml) were spotted on the con peaks (mass, intensity) from the entire set of real spectra, ductive anodized aluminum Surface and air dried. Spots Selecting 350 whose match scores were at a significance were analyzed by a Voyager-DE-STR-MALDI-TOF level of p-0.05. We compared peptides and their match mass spectrometer. For comparison, the same peptides ing sequences from the real spectra to randomly were subjected to conventional MALDI analysis using matched peptides from control spectra to analyze prop a-cyano-4-hydroxycinnamic acid as a matrix. A porous erties of peptides that correlate with peak intensity, structure is necessary for ionization of analytes in including composition and N or C-terminal residues. matrix-free LDI-MS (R1). In the present work we have Since there is a bias in the spectra where smaller peptides grown some hexagonal porous alumina structures using have higher average intensities, we divided the peptide thin films of Al on glass substrates. The as grown Al film masses into four distinct mass ranges for independent thickness were 0.3, 0.5 and 0.7 Lum. Utilizing Al film analysis. In each mass range, we divided peaks into three made the anodization process trivial by not being con intensity categories (high, medium and low) based on cerned on the tedious process of mechanical and elec thresholds picked to create an equal distribution of inten trochemical polishing which is an essential pretreatment sities in each category for each mass range. Comparing step for anodizing directly on bulk Al substrates. In other the amino acid distribution in real peptides versus ran (non-MS) work on nanostructured alumina films, multi domly-matched peptides revealed a strong negative cor step anodization processes are often used on Al Sub relation between peak intensity and the presence of both strates to obtain more uniform porous structures. How cysteine (C) and tryptophan (W). On the other hand, ever, we have shown some promising results using a valine (V) and methionine (M) tend to be favored in high single step anodization process on the Smooth surfaces intensity peaks. Though we expected to see the acidic of Al film with no pretreatment step. Thickness variation residues aspartic acid (D) and glutamic acid (E) corre and anodization at different Voltages have been exam sponding with high peak intensity due to their negative ined to see the effect of pore depth and diameter on MS charge, no such trend was observed. At the N-terminal signal intensity. Samples anodized at 50V gave no pep position, Some of the same trends held as for composi tide signals. Films anodized at 60V and 90V gave peak tion, though with significant differences. Methionine intensities comparable to those with conventional showed an opposite, negative correlation with peak MALDI, however, higher laser intensity was required. intensity when at the N-terminus. Proline (P), tryp Both 60V and 90V anodized samples showed similar tophan (W), and cysteine (C) were also disfavored, results indicating less effect of pore diameter within a whereas valine (V), threonine (T), histidine (H), pheny range of 75 to 120 nm. Thickness (depth of pores) com lalanine (F), isoleucine (I), and alanine (A) all favored parison Suggested that a 0.3 um film is not suitable for peaks of high intensity when at the N-terminus. Of the MS analysis, as the laser flux tends to burn out the two residues found at the C terminus of tryptic peptides, Surface with each shot and Subsequently decreasing the arginine (R) was correlated with high intensity peaks signal intensity. Degradation of signal intensity with whereas lysine (K) was found more commonly in low time was also studied. A 15 days old alumina film did not intensity peaks. Our data indicate that composition of US 2008/0220441 A1 Sep. 11, 2008 11

peptides plays a significant role in peak intensity and analyses of complex proteomic mixtures suggest that hence the likelihood of peptide observation in MALDI desorption/ionization of high mass proteins is much less TOFMS. These data can be used as an additional feature efficient than for lower mass peptides. The equilibrium to improve protein identification methods.” model of the MALDI process Suggests that analyte ion 0054 Advances in MALDI of small molecules using ization proceeds via thermodynamically driven gas surfactants as matrix co-additives', by David C. Grant; phase ion-molecule reactions within the plume of laser and Robert J. Helleur, who stated that "Matrix-assisted desorbed material and, hence, that the primary limitation laser desorption/ionization time-of-flight mass spec to obtaining MALDI ion signals from high MW proteins trometry has been innovative in the analysis of macro is likely related to inefficient desorption of these com molecules. However, it is still developing as a technique pounds. If true, alternate approaches that lead to for Small molecule analysis. The main reason for this is improved desorption of these species within the MALDI the abundance of matrix-related ions in the low mass plume should yield enhanced high molecular weight range of the spectra. The Surfactant cetyltrimethylam protein MALDI ion signals. We have explored this monium bromide (CTAB) has previously been used by hypothesis through the use of various desorbable sub another group as a matrix Suppressor. When added to the layers onto which conventional protein MALDI samples matrix C-cyano-4-hydroxycinnamic acid (CHCA) at an are deposited. Sublayers for SA-MALDI were chosen appropriate molar ratio it has been shown to selectively from a group of hydrophobic polyaromatic hydrocar Suppress matrix ions. Our research expands on this bons. The sublayers were chosena) to be insoluble in the effect by examining a wider variety of surfactants for the matrix and analyte solvents, b) to absorb at 337 nm, c) to analysis of peptides, cyclodextrins, and Small phenolic have no easily donatable protons and d) to have a range compounds such as flavonoids and flavones. Experi of IEs above and below those of typical MALDI matri ments were performed on a Voyager DE-PRO MALDI ces. MALDI MS and SA-MALDI MS analyses were TOF. Analytes were dissolved in 4:1 MeOH:HO (v/v) performed using various peptides and proteins ranging and pre-mixed with CHCA matrix. Each analyte was in MW from 1,200 to 150,000 Da. Conventional dried tested separately with seven surfactants: hexyltrimethy droplet sample preparation was employed, either lammonium bromide, dodecyltrimethylammonium bro directly on the stainless steel MALDI target or on the mdide, cetyltrimethylammonium bromide (CTAB), tet sublayer coated MALDI target. Similar experiments rabutylammonium bromide, decamethonium bromide, were performed using peptide?protein mixtures and, Triton X-100 and sodium dodecyl sulfate (SDS). Each finally, using a crude protein extract from cyanobacteria. Surfactant was mixed with the analyte-matrix solution at The preliminary studies performed clearly demonstrate varying mole ratios to examine the effect of Surfactant that a significant enhancement in the peptide?protein concentration of analyte signal. The parameters moni MALDI ion signal is achieved for SA-MALDI as com tored including analyte resolution, signal-to-noise, peak pared with the conventional dried droplet sample prepa area and intensity. Mixtures of analytes were then tested ration. For every peptide?protein tested between the with each Surfactant. Finally, analysis of phenolic com MW's 1,200 to 150,000 Da a signal enhancement of 1-2 pounds in wine, green tea, and blueberry extracts were orders of magnitude was achieved when using selected undertaken to illustrate real sample applications. Mass Sublayer compounds. The most significant enhance spectra of standard peptides, phenolic acids and other ments were observed for the higher MW proteins. Fur low mass molecules (m/z<500) demonstrate improved thermore, consistent with predictions of the equilibrium mass resolution by 15-45% using appropriate Surfac model of MALDI, the preliminary experiments also tants. Surfactant-mediated MALDI-TOF-MS has also showed a strong dependence of the Sublayer enhance been evaluated for Small molecule quantitative analysis ment on the IE of the sublayer being greater than that of using a second analyte as an internal standard. In one the MALDI matrix. This effect is consistent with the experiment, p-coumaric acid (m/z, 147.30) was analyzed possibility of the Sublayer acting as a "charge sink’ and using quercetin (m/Z303.45) as an internal standard and inhibiting protonation of the analyte i.e. if the IE of the the resulting calibration curve displayed good linearity sublayer is lower than that of the MALDI matrix then an (R=0.9872). Surfactants tested showed promising electron transfer between the photoionized matrix mol results as matrix-ion Suppressors, as spectra were mostly ecules and the sublayer will occur leading to loss of the free of all matrix ions, and displayed low background matrix ions necessary for analyte protonation. Finally, noise at the appropriate molar ratio. It was found that a preliminary experiments suggest that SA-MALDI will matrix:analyte:surfactant ratio of approximately 1000: be particularly useful for complex mixture analysis. 20:1 gave the best spectra in most cases. In some cases, Enhancements of both low MW and high MW signals of ion Suppression was observed by using even lower up to an order of magnitude are observed for both control amounts of surfactant (10000:20:1). Surfactant-medi mixtures of peptides/proteins and for the complex pro ated MALDI showed promise in analysis of analyte tein mixture derived from the cyanobacteria source.” mixtures as well as real samples containing phenolic 0056 “Sensitive and reproducible detection of peptides compounds. Several were identified and Some quantita by Maldi-TOF MS using self-assembled monolayer tively measured by MALDI. Their identity was con (SAM)-based chips—specifications and applications.” firmed by LC-MS. These results indicate that surfactant by Udo Roth; Holger Röhl; Matthias Gluckmann; mediated MALDI may be a good technique for analysis Thorsten Jaskolla; Michael Karas; Kerstin Steinert; and of small molecules.” Karsten Reihs, who stated that “Sensitivity, mass accu 0055 “Sublayer Assisted MALDI (SA-MALDI): Prac racy, and reproducibility are prerequisites for efficient tical Applications and Fundamental Studies.” by Zaneer MALDI-MS analyses used in current quantitative pro M. Segu; and Gary R. Kinsel, who stated that “MALDI teomic work-flows. Our approach consists of a novel US 2008/0220441 A1 Sep. 11, 2008 12

technology for peptide sample preparation using plates for Such analyses, time consuming optimization proce with pre-deposited matrix spots of extra-fine Sub-micron dures are needed before a study can commence. The goal size CHCA crystals prepared by vacuum sublimation on of this study was to determine the trends of matrix/ an ultraphobic surface. Such a design enables the reli- Solvent preference for drugs within a class. A model has able application of nanoliter Volumes of analyte solu- been developed that provides a method for analyzing a tions and facilitates highly reproducible signal detection large number of drugs within a class and across classes. in the low attomole range. To provide a platform for Using the identified trends, sample preparation of dosed high-resolution LC-MALDI-TOF, a high-density array tissue will have a guideline of matrix/solvent preference chip accommodating up to 1600 spots is Supplied. We for analysis by MALDI MS/MS, saving time and present the results of our investigation on the effect of resources. Liver tissue was excised from control (non the properties of the CHCA matrix crystals on the initial dosed) and Olanzapine (OLZ; 8 mg/kg), Spiperone Velocity of the peptide ions and their fragmentation in (SPN; 5 mg/kg) or Propranolol (PPL: 10 mg/kg) dosed MS/MS experiments. Sensitivity, mass accuracy, and Fischer 344 mice. Using a cryostat, tissue was sectioned reproducibility were assessed using different volumes (20 um) and thaw-mounted onto gold-coated MALDI and concentrations of a peptide mixture spotted onto a target plates. For the prediction model, 1 Jul of 1.5 g/ml Mass SpecTurbo Chip with 192 spots. Special attention of a drug standard was spotted on to a MALDI plate, was paid to the flatness of the target and its proper allowed to dry, and then covered with control liver tis electrical ground connection. For LC-MALDI analysis, sue. Sinapinic Acid (SA), 2,5-dihydroxybenzoic acid tryptic digests were separated using a reversed phase (DHB) and a-cyano-4-hydroxycinnamic acid (CHCA) (C18) HPLC-column. Samples were spotted (Probot, matrices were prepared at 25 mg/ml into various binary LC Packings) on a high-density Mass SpecTurbo Chip combinations of acetonitrile, methanol, isopropanol and (1600 spots). Prior to MS analysis, the air-dried spots water. Matrix combinations were spotted onto control were treated with 15 mMammonium dihydrogen phos- and dosed tissue sections for MS/MS analysis by an phate to efficiently reduce the formation of matrix clus- oMALDI-Qq-TOF-MS. Purportedly, matrix/solvent ter ions. The initial velocity was determined by the preferences rely on extraction of drug from tissue and delayed extraction method in a linear two-stage accel- the drug's ability to co-crystallize with matrix. Our eration TOF system. Experiments were carried out using model mimics extraction of drug from dosed tissue. In MALDI-TOF instruments from Bruker (Reflex III) and order for drug signal to be detected, the Solvent must Applied Biosystems (DE-Pro, 4700, 4800). In the sen- extract the drug through the tissue so that it may co sitivity trial, detection of peptide amounts, which were crystallize with the matrix. Dosed tissue sections were applied from a standard dilution series, was achieved spotted with each matrix/solvent combination to deter down to the attomole? spot range. A mass accuracy of an mine the optimal conditions for analysis. For each drug average mass deviation of less than 10 ppm for each spot analyzed, transitions from parent to major fragmentions was routinely obtained by external mass calibration were monitored to avoid matrix signal interference. using the four corner spots of the array. MS/MS experi- Results from the OLZ (m/z. 313->256) dosed tissue ments analyzing attomole amounts of peptides delivered showed that signal was seen with both CHCA and DHB fragment spectra that provided sufficient information for matrices; however, optimal sensitivity by an order of the unambiguous identification of peptides. Reproduc- magnitude was achieved using CHCA in 50% acetoni ibility of sample preparation yielded RSD values of trile. The model predicted the same optimal matrix/sol typically less than 10-20% depending on the peptide. vent as for OLZ dosed tissue, but demonstrated a two The benefits of sensitivity, mass accuracy, and reproduc- fold increase in sensitivity not seen in the dosed tissue. ibility provide an optimal combination for high through- Similar drugs within the benzoazepine class. Such as put LC-MALDI experiments. We show that peptide carbamazepine (m/Z 237-> 194) and clozapine (m/z identification can be significantly increased compared to 328->272), preferred CHCA. Drugs in the f-andrener standard procedures using stainless steel Substrates. Due gic blocker class, such as PPL (m/z. 260-> 116) and to the Sublimation deposition technique used for matrix metaprolol (m/z. 268-> 116), exhibited preference for spot preparation, we obtain very small CHCA crystals of CHCA based on the model; however, no clear difference a typical crystal size of less than 1 micron. We found that in sensitivity was observed for various solvent condi these spots yield significantly higher initial Velocities of tions. This was also seen in the PPL dosed tissue. Dosed the emitted peptide ions in the range of 650 m/s com- SPN tissue (m/z 396->165), indicated an affinity for pared to about 300 m/s for standard dried droplet prepa- DHB independent of solvent. This preference was also rations. Higher initial velocities may significantly influ- predicted by the model. Preliminary data indicates that ence fragmentation processes by more effective matrix/Solvent trends do exist within a drug class. The expansional cooling during ion formation. Results con- advantage of the model allows us to effectively mimic cerning the relationship between the initial velocity and the behavior of dosed tissue, while avoiding the need to the peptide fragmentation process will be presented and dose and sacrifice animals for each determination of discussed.” optimal matrix/Solvent combination. The model is being 0057 "Predicting matrix conditions for drug analysis in extended to butyrophenone (SPN) and B-andrenergic tissue by MALDIMS/MS” by Sara L. Frappier. Sheerin blocker (PPL) classes in addition to other drug classes, K. Shahidi; and Richard M. Caprioli who stated that “It as well as, other tissues such as kidney and brain.” has been previously found that various drug classes have 0058 Focusing chips for MALDI-MS have different preferential matrix/Solvent conditions when analyzing requirements than focusing chips for X-ray fluorescence. dosed tissue by MALDI MS/MS. Since there are no Focusing chips for X-ray fluorescence should preferably not established trends known for matrix/solvent preference interfere with XRF measurement. For example, the chips US 2008/0220441 A1 Sep. 11, 2008

should have a limited amount of chemical elements that may Symposium Proceedings 2006, 893, 183-188; all incorpo interfere with the sample being measured. Preferably the rated herein by reference. The PAD process may be used to focusing chip for use with X-ray fluorescence should have an deposit patterns of different materials, including metallic amount of a chemical element that produces less than 25% of phase metals, metal oxides, and metal nitrides. Using PAD, the signal of the sample being measured, when measured for different regions of hydrophilic materials and hydrophobic at least one of the elements that are present in both the focus regions on a Substrate, typically a silicon or aluminum Sub ing chip and the sample. More preferably, the focusing chip Strate. for X-ray fluorescence is free of elements that may interfere 0062 Another convenient method for preparing focusing with the sample being measured. Typical elements to be mea chips uses the formation of hydrophilic and hydrophilic Sured include Sulfur, fluorine, phosphorus, chlorine, bromine, regions on a Substrate using Supported mesoporous silica. iron, Zinc, magnesium, calcium, titanium, Scandium, and This method is described in A. M. Dattelbaum and S. Iyer, platinum. The metal Substrate that the focusing chip is Sup "Surface-assisted laser desorption ionization mass spectrom ported on should not contain elements that have X-ray emis etry.” Expt. Rev. Proteomics. 2006, 3(1): 153-61; and in U.S. sion spectral peaks in the region of interest, and preferably do Pat. No. 6,958,480, “Sample desorption/ionization from not have X-ray emission spectral peaks between 2 KeV and 3 mesoporous silica”, published Octover 25, 2005 to Srinivas KeV. Iyer and Andrew Dattelbaum; and Nancy H. Finkel et al. 0059 Focusing chips for X-ray fluorescence should pref “Ordered Silicon Nanocavity Arrays in Surface-Assisted erably be thin. Thick chips or slides cause scattering in the Desorption/Ionization Mass Spectrometry” Analytical X-ray portion of the electromagnetic spectrum. Preferably, Chemistry, 77 (4), 1088-1095, 2005 incorporated herein by the chips are less than 500 microns thick, and more preferably reference. the chips are less than about 50 microns thick. Focusing chips 0063. In each of the cases described above, the MALDI as described in the MALDI-MS literature, for example from focusing chips is preferably modified such that it is formed on the list of presentations at the 54th ASMS Conference on a thin substrate, preferably less than 500 microns thick and Mass Spectrometry, May 28-Jun. 1, 2006, Washington State more preferably less than 50 microns thick. Convention & Trade Center, Seattle, Wash., should be re 0064. The XRF focusing chip is used by depositing a manufactured on thin supports to facilitate their use with sample, which typically consists of an aqueous sample of a X-ray fluorescence. protein or nucleic acid, which has been optionally modified 0060. The size of each hydrophilic region is important. by addition of an inhibitor, co-factor, metal, protein, Sugar, or Preferably, each hydrophilic region has an area between 75 other chemical. The sample is allowed to dry, and then the square picometers (equivalent to a spot with a diameter of focusing chip with the deposited Sample is irradiated with X-rays and any fluorescence of X-rays are measured. about 10 microns) and 3.6 square microns (equivalent to a 0065. The sample on the X-ray focusing chip may be spot with a diameter of about 4 millimeters). conveniently measured using an X-ray fluorescence instru 0061. One convenient method for preparing focusing ment with a monocapillary focusing optic, polycapillary chips uses polymer assisted deposition (PAD), described in: focusing optic, a collimator, a microfocus X-ray tube, a syn Published Patent Application 2005.0043.184, “Polymer-as chrotron X-ray source, a linear accelerator X-ray source, a sisted deposition of films.” published Feb. 24, 2005, to Tho rhodium X-ray tube, a molybdenum X-ray tube, a chromium mas M. McCleskey et al.; Published Patent Application X-ray tube, a silver X-ray tube, a palladium X-ray tube, a 20050008777, “Polymer-assisted deposition of films,” pub monochromatic X-ray source, a polychromatic X-ray source, lished Jan. 13, 2005, to Thomas M. McCleskey et al.: “Poly a polarized X-ray Source, a confocal X-ray fluorescence spec mer-assisted deposition of metal-oxide films.” Jia, Q. X. trometer, a PIN diode detector, a semiconductor X-ray detec McCleskey, T. M.; Burrell, A. K. Lin, Y.; Collis, G. E.; Wang, tor, a germanium or doped germanium X-ray detector, a sili H. Li, A. D. Q.: Foltyn, S. R. Nature Materials 2004, 3(8), con or doped silicon X-ray detector, a wavelength dispersive 529-532.: “Epitaxial growth of Eu2O3 thin films on LaAlO3 X-ray fluorescence spectrometer, an energy dispersive X-ray substrates by polymer-assisted deposition Lin, Y.; Wang, H.; fluorescence spectrometer, total reflectance X-ray fluores Hawley, H. E.; Foltyn, S. R. Jia, Q. X. Collis, G. E.; Burrell, cence spectrometer, and the like. A. K. McCleskey, T. M. Appl. Phys. Lett., 2004, 85(16), 0066. If total reflectance x-ray fluorescence (TXRF) is 3426-3428; "Structural and dielectric properties of epitaxial employed with the present invention, the preferred substrates Ba1-xSrxTiO3 films grown on LaAlO3 substrates by poly are quartz, lucite, mylar, silica, Silicon with a smooth Surface mer-assisted deposition Lin, Y.; Lee, J-H.; Wang, H. Li, Y.: for sample deposition. Foltyn, S.R., Jia, Q.X.; Collis, G. E.; Burrell, A. K.; McCles key, T. M.: Appl. Phys. Lett., 2004, 85(21), 5007-5009: Beam Size “Green luminescent zinc oxide films prepared by polymer assisted deposition with rapid thermal process” Lin, Y.; Xie, 0067. In X-ray fluorescence microscopy, we have found J.; Wang, H. Li, Y.: Lee, S.Y.; Foltyn, S. R.: Crooker, S.A.: that the most efficient (strongest signal with lowest noise) Jia, Q. X.; Burrell, A. K. McCleskey, T. M. Thin Solid Films, X-ray beam size, ceteris paribus, is one that is essentially 2005, 492(1-2), 101-104.: "Conformal coating of nanoscale matched to the sample size. This situation has not arisen features of microporous AnodiscTM membranes with zirco previously because the samples used in the past have been nium and titanium oxides.” Shukla, P.; Minogue, E. M.: larger than the beam size, so many systems use a small beam McCleskey, T. M.; Jia, Q. X. Lin, Y.: Lu, P.; Burrell, A. K.: size and rastering or scanning across the sample. Also, many Chemical Communications, 2006, (8), 847-849.: “Polymer samples are not homogenous, so having a beam size matched assisted deposition (PAD) of thin metal films: a new tech to the sample size has not previously made much sense. nique to the preparation of metal oxides and reduced metal 0068 For the biomedical samples we have analyzed, the films.” Shukla, P.; Lin, Y.; Minogue, E. M.; Burrell, A. K.: samples are generally circular and tend to have diameters McCleskey, T. M.; Jia, Q.: Lu, Pi. Materials Research Society between 40 um and 2 mm (i.e., areas of about between 1 US 2008/0220441 A1 Sep. 11, 2008 square nanometer and 3 square microns). These samples are http://www.vsep.com/pdf/PolymerDiafiltration.pdf. This also homogenous or otherwise have no need to be sampled in process is amenable to multiplexing using a well plate format, Subregions. In Such cases, we have found that matching the such as a 96-well, 384-well, or 1536-well plate format. Sepa beam size to the spot size provides the strongest signal to rations systems such as Zeba 96-well plates available from noise ratio. Thus, a preferred X-ray fluorescence source for Pierce Biotechnology Inc., PO Box 117, Rockford, Ill., measuring a sample comprises an X-ray Source, where the 61105, are particularly convenient. As can be seen in the transmitted X-ray beam has a cross-sectional area essentially following table, Zeba well-plates function across a wide the same surface area as the sample. Thus the beam preferably range of concentrations of Bovine Serum Albumin, where the has a cross-sectional area of between about 1 square nanom units for the numbers in the table are percent mass recovered, eter and 3 square microns. “Matching” would preferentially unless otherwise noted: be as close as match as practical, but an imperfect match where the beam has a cross-sectional area of between 25% and 250% of the surface area of the sample is also acceptable. 0069. This area matching may be accomplished in rare 5 10 25 50 cases by having an X-ray source whose transmitted beam micromolar micromolar micromolar micromolar cross-sectional area matches the sample area without any 10 39 +f- 21% 48 +/- 2% 63+f- 5% 62 +/- 3% microliters modification of the beam. More typically, the beam size will 2O 79 +f- 11% 70+f- 2% 78+f- 2% 83 +f- 2% have to be modified to match the sample size. Modification is microliters typically carried out by means of focusing optics or by a 30 87+f-3% 79 -f- 4% 80+f- 2% 90 +/- 4% collimator. Thus, the source further comprises a focusing microliters means or collimator disposed between the source and the 40 103 +f-3% 95+f- 1% 89+f- 8% 98 +f- 5% sample. microliters Sample Composition 0072 The single-plexed or multiplexed gel filtration chro matography process may be expedited using a centrifuge, 0070. Many samples, such as proteins, require a buffer to such as a the IEC Multi and Multi RF Centrifuges with a maintain the pH within a particular range (i.e. a pH buffer), or Microplate Rotor Available through Fisher Scientific, catalog to maintain the redox state of a chemical (i.e. a redox buffer). #05-375-77, Liberty Lane, Hampton, N.H. 03842, manufac Many buffers contain elements which might interfere with the tured by International Equipment Company; or a vacuum measurement of the chemical. The buffer should preferably manifold. Such as a Vacuum apparatus Such as the Multi be free of at least one chemical element having an atomic Screen Vacuum manifold with Direct Stack from Millipore, number of greater than four, where that chemical element is 290 Concord Road, Billerica, Mass. 01821, attached to a present in the chemical. The buffer should also preferably be standard vacuum pump (Catalog #WP61 11560) also avail free of at least one chemical element having an atomic num able from Millipore. Separation may be performed using ber of greater than four, where that chemical element is ZipPlate(R) micro-SPE Plate and MALDIspot Accessories present in the receptor. The buffer should more preferably be also available from Millipore, as well as similar protein free of at least one chemical element having an atomic num desalting well plates and DNA destaining well plates. Sepa ber of greater than eight, where that chemical element is present in the chemical. The buffer should also more prefer rations are preferably carried out in less than 30 seconds at 4 ably be free of at least one chemical element having anatomic degrees Celsius, as described in Annis DA et al. An affinity number of greater than eight, where that chemical element is selection-mass spectrometry method for the identification of present in the receptor. The buffer should be free of surfac Small molecule ligands from self-encoded combinatorial tants or detergents that contain Sulfur or phosphorus. The libraries: Discovery of a novel antagonist of E. coli dihydro buffer should preferably be free of at least one of the follow folate reductase. International Journal of Mass Spectrometry. ing chemicals or functional groups: dimethylsulfoxide, thi 2004, 238:77-83. An alternative method of separation is ultra ols, sulfate anion, Sulfonate anions, chloride anion, bromide filtration, Such as is described in the following examples: anion, fluoride anion, iodide anion, perchlorate anion, phos phate anion, and phosphonate anions. The buffer preferably FIRST EXAMPLE does contain one or more of the following chemical or func 0073. We measured the interaction between biotin and tional groups: amine, imine, nitrate anion, nitrite anion, avidin to demonstrate that RPM could quantify the sulfur ammonium cation, and iminium cation; these chemicals offer containing Small molecule (biotin, CoHNOS) over the the correct buffering properties with minimal x-ray fluores Sulfur content of a protein (tetrameric avidin, Sigma-Aldrich, cence interference. Most preferably, the buffer consists of an 16 sulfur atoms, see Korpela J. Avidin, a high affinity biotin ammonium nitrate Salt Such as tris(ethanol)amine nitrate, also binding protein, as a tool and Subject of biological research. known as tris nitrate. Medical Biol. 1984, 62:5-26). Previous studies have shown 0071. The proteins to be used with the present invention that the ratio of sulfur in avidin-biotin:avidin is 19.5:16, or are preferably purified to remove chemicals which are not 1.22, see Green NM. Purification of Avidin. Meth Enzymol. chemically bound or which are loosely bound to the protein. 1970, XVIII(A):414-417. We incubated 500 micrograms of Loosely bound is defined in this paragraph as meaning having avidin in 1.0 ml of 0.20 millimolar biotin at pH 8.0 for 5 a binding affinity that is weaker than about one (1) millimolar. minutes and then centrifuged the sample for 3 hours at 7000 This desalting step may be conducted conveniently using gel g using a Centricon YM-3 resulting in a concentrated avidin filtration chromatography or size exclusion chromatography, biotin sample of 25-50 ul. We diluted the sample to 0.75 ml in such as using a Sephadex G25 or Sephadex G50 column. TRIS buffer (pH 8.0), centrifuged for 2 hours at 7000 g, and Desalting may also be accomplished using dialysis, including repeated this process twice. We treated an avidin control Vibratory Shear Enhanced Process dialysis described in sample identically. We used RPM to measure the sulfur con US 2008/0220441 A1 Sep. 11, 2008

tent of the avidin-biotin complex and the avidin. We con the measurement requirements of the technique. The mea firmed that the amount of avidin in each sample was identical Surement technique can measure samples containing as little using bicinchoninic acid protein assay kit (Pierce). As pre as about 100 femtograms of the chemical elements to be dicted, the avidin-biotin complex contained 1.2 times the measured. More conveniently, measurements are obtained on sulfur than the avidin alone as measured by RPM. This set of samples containing between ten nanograms and one micro experiments demonstrated that RPM can measure strong non gram of the element to be measured. Robotic pipettes or covalent interactions and use fluorescence ratios to determine automated biological printers may be used, such as a BioDot binding even when the protein and analyte have only a shared BJQ3000 BioJet Quanti 3000 or BJP3000 BioJet Plus 3000, RPM atom (in this case, sulfur). available from BioDot, Inc, 17781 Sky Park Circle, Irvine, Calif. 92614. Acoustic printers may be conveniently used, SECOND EXAMPLE such as the Echo 555 Liquid Handler, the Echo 550 Liquid 0074. Our preliminary data show that RPM measures non Handler, and the PortraitTM 630 MALDI Reagent Multi-Spot covalent protein-inhibitor complexes. We used di-zinc ami ter, available from Labcyte Inc., 1190 Borregas Avenue, nopeptidase (aAP) and its competitive inhibitor leucine phos Sunnyvale, Calif. 94089. phonic acid (LPA). LPA binds to aAP with a Ki of 6.6 uM at 0076 Samples should be dried in a manner that promotes pH 8.0, see Stamper Cetal. Inhibition of the aminopeptidase formation of an evenly distributed spot. Drying a sample of from Aeromonas proteolytica by L-leucinephosphonic acid. protein into an evenly distributed spot is extremely challeng Spectroscopic and crystallographic characterization of the ing. Proteins affect the Surface tension of water, especially at transition state of peptide hydrolysis. Biochemistry, 2001, high protein concentrations and Small solvent Volumes, i.e. 40:7035-7046. We incubated 500 micrograms of aAP in 1.0 the exact conditions for drying. This problem is well known in mls of 0.20 millimolar LPA (>10xKi) at pH 8.0 for 5 minutes. the art, and has prompted the development of highly expen We centrifuged the aAP-LPA sample for 3 hours at 7000 g sive solutions such as the Labcyte acoustic equipment men using a Centricon YM-3 resulting in a concentrated sample of tioned above, and described in “The Echo 550tm Delivering 25-50 ul. We diluted this sample to 0.75 ml in TRIS buffer (pH Results in Screening.” by Jennifer Zewinski, available at 8.0), centrifuged for 2 hours at 7000 g, and repeated this http://www.labcyte.com/aboutus/publications/Zewinski process twice. We Subjected two negative control samples to (BMS) EchoPresentation.pdf and in "Acoustic Non-Contact the same filtering conditions described above: The first con Dispensing-The Right Choice for UHTS.” By Timothy P. trol was 1.0 ml of 0.20 millimolar LPA, and the second Spicer, available at http://www.labcyte.com/news/events/ control was 200 micrograms of avidin and 1.0 ml of 0.20 Spicer'9620Presentation%20for%20SBS%202004%20 millimolar LPA to test the possibility of electrostatic and revised%208 19 041.ppt; and by “Pharmacological Evalu hydrophobic interactions between LPA and non-specific pro ation of Different Compound Dilution and Transfer Para tein. We measured phosphorus was measured in the aAP-LPA digms on an Enzyme Assay in Low Volume 384-well For complex in a 1:2 ratio; no phosphorus was observed in the mat, by Tim Spicer, Yvonne Fitzgerald, Neil Burford, Sandra control samples. This set of experiments demonstrated that Matson, Moneesh Chatterjee, Mark Gilchrist, Jim Myslik and RPM can measure weak non-covalent interactions (6.6 Jonathan O'Connell, available at http://www.labcyte.com/ micromolar) and use fluorescence ratios to determine binding aboutus/publications/BMSposterDDT2005-2.ppt. While no when the protein and analyte have different RPM atoms (in ideal solution has been found, preferable solutions include the this case, Zinc and phosphorus). following. One preferable approach to protein deposition uses focusing chips (described above), which promote even Sample Deposition drying of protein solutions. Another convenient approach to protein deposition is to digest the protein using pepsin or 0075 Samples may be conveniently deposited on sub trypsin or other proteases; this approach changes the Surfac strates in several ways. One very convenient manner for tant properties of the protein and promotes more even drying sample deposition is deposition of a Volume of Solution con of samples. Other matrix modifying chemicals, such as acetic taining the sample using a pipette or Syringe. Pipettes are acid, trifluoracetic acid, detergents, salts (especially salts that especially preferred because they may be multiplexed. Such do not contain some or all of the chemical elements being as an EppendorfR Research Multichannel Pipette catalog measured in the chemical or the protein) or Surfactants, pro number 0224.52002, available from EppendorfR North mote the even drying of samples; these matrix modifiers are America Inc. One Cantiague Road, P.O. Box 1019, Westbury, thought to cause proteins to denature or to adopt a molten N.Y. 11590-0207. The amount of sample to be deposited is globular state by disrupting protein folding through the dis important. Large sample solution Volumes tend to dry slowly ruption of hydrogen bonds, saltbridges, disulfide bonds, and and unevenly. Small sample Volumes contain only small other covalent and non-covalent interactions that affect pro amounts of sample. Preferably, the sample solution is depos tein folding. This molten globular state must be achieved ited in a volume of between 1 nanoliter and 50 microliters, without precipitation of the protein, which leads to inhomog and more preferably the sample solution is deposited in Vol eniety in the sample. Proteins may also be denatured or ren umes of between 10 nanoliters and 10 microliters. Most pref dered into their molten globular state by heating the solutions erably, the sample solution is deposited in Volumes of of the sample, preferably above 90 degrees Celsius, but at between about 25 nanoliters and about 8 microliters. The least above about 40 degrees Celsius, depending on the pro sample concentration is also important. The sample solution tein and its thermal stability. High quality protein spots may that is deposited preferably contains between 100 picograms be generated by heating under an infrared lamp, or a Sun lamp, of protein and 1 gram of protein. More preferably, the sample or a halogen lamp, or any lamp with a wattage above about 55 Solution that is deposited contains between about 1 nanogram watts. High quality protein spots may also be obtained when of protein and 1 milligram of protein. The reason for this the sample is dried while being centrifuged, preferably also sample mass requirement is to balance the cost of protein and under reduced pressure. Centrifugation under at least apartial US 2008/0220441 A1 Sep. 11, 2008

vacuum is particularly convenient for Samples that are mul mycin; Venlafaxine; Idarubicin; Chlorthalidone; Tizanidine: tiplexed, because the whole set of multiplexed samples may Flecamide: Uracil Mustard; Dichlorphenamide: Adenosine: be dried under identical conditions. Valsartan; Nandrolone Phenpropionate; Ouabain; Quinidine: Methacycline; Olanzapine; Isotretinoin; Balsalazide. Amox X-Ray Sources apine; Vitamin D4 (Dihydrotachysterol); Exemestane: Rilu 0077. Many X-ray sources will function with the present Zole; Tolterodine: Citalopram; Cidofovir; Delavirdine: invention. Rhodium and molybdenum X-ray Sources are com Nilutamide: Rofecoxib; Sulfasalazine; Nitroglycerin; Thia monly employed. Biological samples and pharmaceutical mylal; Cilostazol; Pramipexole; Methoxsalen: Oxymor samples frequently contain the elements phosphorus, Sulfur, phone. Succinylcholine; Carbidopa; Mupirocin; Remikiren: and chlorine. It is preferable that the X-ray sources do not Captopril; Levobunolol; Phenindione: Probenecid; Solifena generate noise or excessive scattered X-rays in the region of cin Succinate; Almotriptan; TolaZoline; Arsenic Trioxide; the spectrum that is of most importance. Therefore, it is Atenolol; Trifluoperazine; Clonidine: Sertraline; Tub preferable to use a chromium, palladium or silver X-ray ocurarine; Propantheline; Sirolimus; Prilocalne; Clarithro source. If the sample is known or believed not to contain mycin; Isoproterenol; Valdecoxib; Phenobarbitone; Doxoru chlorine, or if the chlorine spectrum is not needed for the bicin: Oxaliplatin: Risperidone: Proguanil; Oxyphenonium; analysis, then a rhodium source may be used. Molybdenum Sulfadiazine; Nitrofurantoin: Lercanidipine: Propranolol; X-ray sources are less efficient than other X-ray tubes at excit Carteolol; Cefadroxil; Prednisolone: Reboxetine; Caspofun ing phosphorus, Sulfur, and chlorine, and are less preferred. gin; Nicotine; Gemcitabine; Pentostatin: Capecitabine; Vita Most preferably, the X-ray tube has a characteristic K-alpha or min B6 (Pyridoxine); Leflunomide; Galantamine; Rifampin; L-alpha line at or above about 2.838 KeV and less than about Metoprolol; Streptozocin; Metaproterenol; Crotamiton; Isof 9.441 KeV. X-ray M lines are frequently broad and less effi lurane; Cyclobenzaprine; Gentamicin; Morphine; Abacavir; cient. The X-ray source preferably does not have an M line Torasemide: Pimozide. Sevoflurane; Naratriptan; Meman above 2. 120 KeV. X-rays that impinge on the sample may be tine; Buspirone; Olmesartan Medoxomil: Cevimeline; pip generated by X-ray tubes directly, or indirectly by the excita erazine; Emtricitabine; Amitriptyline; Phenprocoumon; tion of a target by X-rays. Timolol; Suprofen; Ibandronate; Netilmicin; Glyburide: Enflurane; Levothyroxime; Paramethadione; Topiramate: Chemicals Etoposide; Didanosine; Phenyloin; Mexiletine; Cefaclor; Clotrimazole; Betaxolol; Calcitriol; Bupivacaine: Amoxicil 0078 While this process may be used for many chemicals, lin; Mechlorethamine; Cephalexin; Ethacrynic acid; it is preferable that the chemical to be measured comprises at Acetaminophen; Clomipramine: Ranitidine; Orlistat; Valp least one of the following chemical elements chemically roic Acid; Bisoprolol; Trimeprazine; Paclitaxel; Cladribine; bound to the majority of the chemical: fluorine, phosphorus, Propafenone; Phenmetrazine; Ganciclovir, Aspirin; Zileu Sulfur, chlorine, bromine, iodine, platinum, copper, iron, Zinc, ton; Butalbital; Tolbutamide; Trimetrexate; Picrotoxin; Fro gallium, or gadolinium; in this context, chemically bound is Vatriptan; Ridogrel, Demeclocycline; Enprofylline; Lopera defined as covalent bonds or metal-ligand bonds having a mide; Tacrolimus; Salmeterol: Clofazimine: Alprazolam: bond strength of at least 30 kCal/mole. Moxifloxacin; Vigabatrin; Mitomycin; Cefuroxime; Tridi 0079 Chemicals which may be used with the present hexethyl; Tropicamide; Amiodarone; MometaSone; Thiogua invention include the following, along with any salts and free nine; Lomustine; Gemfibrozil; Bumetanide; Torsemide; bases: Chlorpheniramine; Methimazole; Nelfinavir, Zonisa Famotidine: Propylthiouracil; Isradipine: Flucytosine: mide; Naltrexone; Carmustine: Ifosfamide: Rizatriptan; Mefloquine; Nadolol; Ropinirole; Pentamidine: Tirofiban: Ramipril; Milrinone; Tenoxicam; Apraclonidine; Neomycin; Sertaconazole; Triprolidine: Clobazam; ChlorZoxazone: Gabapentin; Anastrozole; Alitretinoin. Oxytetracycline: Pra Levodopa; Olopatadine; Estradiol; Ritonavir; Triazolam: Zosin; Amifostine; Desipramine; Hydroxyurea; Naloxone; Methscopolamine; Trimethadione: Remoxipride: Quina Kanamycin; CandoXatril; Tramadol; Chlorpropamide; crine; Ethosuximide: Fenfluramine; Ampicillin; Rivastig Oxaprozin; Trichlormethiazide; Sulpiride: Cyproheptadine: mine; Thiethylperazine; Desloratadine; Piperacillin; Vitamin Brimonidine; Tamsulosin; Misoprostol; Pentolinium; Done B12: Fluconazole; Pravastatin; Aminophylline; Dacarbazine: pezil; Itraconazole; Penciclovir; Bicalutamide: Epinastine; Cinnarizine: Vidarabine; Verapamil: Cromolyn; Carbam Trimethaphan; R-mephobarbital; Clavulanate; Nitrofura azepine; Propiomazine; Prednisone; Warfarin; Methylpred Zone; Bethanechol; Losartan; Gemifloxacin; Clonazepam, nisolone; Clomocycline; Tiagabine; Dapsone; Fluvastatin: Atorvastatin: Heparin; Methohexital; Efavirenz: Duloxetine; Fentanyl; Fexofenadine: Palonosetron; Methotrexate: Cyclizine; Methoxamine; Benazepril; Amsacrine: Flutica Meclizine; Zopiclone: Promazine: Cisplatin: Dipyridamole; sone Propionate; Divalproex; Etodolac. Enoxaparin; Indi Epirubicin; Tretinoin, Esomeprazole; Paroxetine; Phenyle navir; Trihexyphenidyl; Tadalafil; Progabide; Pantoprazole; phrine; Diphenoxylate; Dofetilide; Acrosoxacin: Lovastatin: Meperidine; Guanfacine; Sulfamethoxazole; Lansoprazole; Mitoxantrone; Ibuprofen; Celecoxib; Felodipine; Zolmitrip Porfimer; Triamterene; Cocaine; Ribavirin; Theophylline: tan; Zafirlukast; Zanamivir, Sumatriptan; Pyridostigmine; Vitamin C: Dopamine; Minoxidil; Nicardipine; Phenace Glimepiride; Pilocarpine: Procyclidine: Loratadine; Dutast mide: Dexrazoxane: Carvedilol; Hydrochlorothiazide; Phen eride; Mequitazine: Oxycodone: Flupenthixol; Toremifene: termine; Rifabutin; Zolpidem; Tegaserod; Orphenadrine; Vindesine; Trospium; Pemirolast; Ceftriaxone; Conjugated Digoxin; Phenelzine; Aprepitant; Vinorelbine; Cerivastatin: Estrogens: Azithromycin; Doxepin: Oxyphencyclimine; Ral Trimethoprim; Simvastatin: Argatroban; Norgestrel; Per oxifene; Ketoconazole; Nefazodone; Rosiglitazone; Chloro hexyline; Pefloxacin; Indomethacin: Levobupivacaine: Res procaine; Fenofibrate; Physostigmine; Cyclophosphamide; cinnamine; Dicyclomine; Bexarotene; Chlorambucil; Phenylbutazone: Risedronate; Zaleplon; Streptomycin; Irbe Lorazepam, Hesperetin; Melphalan: Acetazolamide; Sartan; Entacapone; Carisoprodol; Domperidone; Halofan Codeine; Pentoxifylline; Dobutamine; Tamoxifen; Dactino trine; Candesartan; Nitrendipine; Triamcinolone; Penicillin US 2008/0220441 A1 Sep. 11, 2008

V: Ciprofloxacin; Fluvoxamine; Vitamin D2 (Ergocalcif Ergoloid Mesylate: Gallamine Triethiodide; Methdilazine: erol); Oxybutynin, Calcidiol; Perphenazine: Raltitrexed: Betazole; Chlorotrianisene; Chlorprothixene; Diphenylpyra Eszopiclone: Mifepristone; Testosterone; Montelukast; line; Chlorothiazide: Hexachlorophene; Buclizine; Adina Allopurinol; Glipizide. Sulfanilamide: Repaglinide; Stavu Zolam; Biperiden: Alfentanil; Bepridil; Benzthiazide; Ethop dine: Protriptyline; Budesonide; Omapatrilat; Clopidogrel; ropazine; Mefenamic acid; Cycrimine; EthoXZolamide; Tolcapone: Omeprazole; Zidovudine: Epinephrine; Sulfac Levallorphan; Methyprylon; Minaprine; Alprenolol; Clid etamide: Bleomycin; Cisapride: Isosorbide Dinitrate; inium: Ethanol; Methylergonovine; Methazolamide: Anileri Sibutramine; Phenylpropanolamine: Mecamylamine; Gli dine; Melatonin; Methoxyflurane; Levomethadyl Acetate; clazide; Cefprozil; Acetophenazine; Methysergide; Phytona Maprotiline; Benztropine; Aminosalicylic Acid; Isoetharine; dione; Triflupromazine; Carboplatin: Chloroquine; Nor Methantheline; Butabarbital; Flurbiprofen; L-Norgestrel; floxacin; Clozapine; Reserpine; Diltiazem; Doxazosin; Fludrocortisone; Metharbital; BenZphetamine; Ethynodiol Brinzolamide: Dihydroergotamine; Levofloxacin; Diacetate; Dicumarol: Desogestrel; Isofluorophate: Levor Lidocaine; Amphetamine; Ondansetron; Chlorpromazine; phanol; Carbinoxamine; Etonogestrel; Disulfuram; Dyphyl Telithromycin; Methadone; Vitamin A: Guanabenz; Troglita line; Dexbrompheniramine; Ambenonium; Acebutolol; Zone; AlfuZosin; Sulfapyridine; Ropivacaine; Ketamine; Acetohexamide; Acetohydroxamic Acid, Acitretin: Ada Mitotane; Vincristine; Phensuximide: Secobarbital; Trimi palene; Adefovir Dipivoxil; Albendazole; Alclometasone; pramine; Cytarabine; Fondaparinux; Ofloxacin; Carbima Alprostadil; Alseroxylon; Amantadine; Amcinonide; Amdi Zole; Idoxuridine: Felbamate; Vitamin D3 (Cholecalciferol): nocillin; Amiloride; Aminocaproic Acid; Aminohippurate; Disopyramide; Terbinafine: Procainamide: Enalapril; Phen Aminolevulinic Acid, Amlexanox: Amodiaquine; Amphot formin; Mephenyloin; Betamethasone; Metaxalone: Piren ericin B; Anagrelide; Anisindione; Anisotropine Methylbro Zepine: Fluorouracil; Sulfametopyrazine; Dolasetron; Amlo mide; Arbutamine; Ardeparin; Atazanavir, Atovaquone; Atra dipine; Daunorubicin; Proparacaine; Quinapril; Selegiline; curium; Atropine; Auranofin, AZacitidine, AZatadine; Fosinopril; Diclofenac; Isosorbide Mononitrate; Meloxicam; Azathioprine; AZelaic Acid, AZelastine; AZlocillin, AZtre Fluoxetine: Apomorphine: Trazodone; Modafinil; Profla onam; Bacitracin: Oxybuprocaine; Bentiromide: Bento vine; Vitamin B3 (Niacin); Ipratropium; Haloperidol; Ben quatam, BenZquinamide; Benzyl Benzoate, Benzylpenicil Zocaine; Ziprasidone; Ritodrine; Voriconazole; Chlorhexi loyl Polylysine; Betanidine; Bimatoprost; Bitolterol dine: Rosuvastatin: Minocycline: Propoxyphene: Primidone: Mesylate; Bortezomib; Bosentan; Bretylium; Bromfenac: Amikacin; Baclofen; Vitamin B1 (Thiamine); Albuterol: Brompheniramine; Butenafine; Butoconazole; Butorphanol Metaraminol; Sildenafil; Temozolomide: Nitazoxanide; Tartrate; Cabergoline; Calcium Acetate; Calcium Chloride: Marimastat; Lisinopril; Alendronate; Zalcitabine; Quinine; Calcium Gluceptate; Candicidin; Capreomycin; Carbachol: Beclomethasone; Lymecycline; Clindamycin; Acyclovir, Carbenicillin; Carboprost Tromethamine; Carphenazine: Cimetidine, Norgestimate; Lamotrigine; Marinol; Tetracy Carprofen; Cefditoren Pivoxil; Cefnmenoxime; Cefnetazole; cline; Pemetrexed: Loxapine; Sotradecol; Dorzolamide: Ceforanide; Cefotaxime; Cefotiam; Ce?piramide: Ceftazi Dexmedetomidine; Irinotecan; Alosetron: Tobramycin; dime; Cephaloglycin; Cephalothin; Cephapirin; Ceruletide: Cefixime: Astemizole; Diphenhydramine; Estrone; Terbuta Chloramphenicol; Chlormerodrin; ChlormeZanone; line; Nifedipine; Hydrocodone; Aminoglutethimide; Nateg Chloroxine; Chlorphenesin; Cloclopirox; Cinacalcet; Cino linide; Fludarabine; Sulfisoxazole; Thioridazine; Doxycy xacin; Cisatracurium Besylate; Clemastine; Clobetasol; Clo cline; Halothane; Pyrimethamine; Famciclovir; cortolone; Clofarabine; Clofibrate; Clomifene; Clorazepate: Promethazine; Nortriptyline: Moclobemide: Primaquine; Cloxacillin; Colesevelam: Colestipol; Colistimethate: Colis Amprenavir, Terfenadine: Hyoscyamine; Furosemide: Flu tin, Cryptenamine; Cyclacillin; Cyclopentolate; Cycloserine; cloxacillin; Mesoridazine; Nimodipine; Encamide: Atomox Cyclothiazide: Cysteamine Bitartrate; Dantrolene; Dapipra etine; Phentolamine; Scopolamine; Nicergoline; Framycetin: Zole; Darifenacin; Deferoxamine; Demecarium bromide: EZetimibe: Sulfinpyrazone; Bupropion; Bromocriptine: Deserpidine; Desflurane; Deslanoside; Desoximetasone: Saquinavir. Prochlorperazine; Estramustine; Vitamin B2 (Ri Dextrothyroxine; Dezocine; Diatrizoate; Diazoxide: boflavin); Medroxyprogesterone; Papaverine; BenZonatate; Dibucaine; Dicloxacillin; Dienestrol; Diethylcarbamazine: Cetirizine; Metronidazole; Finasteride: Fluphenazine: Pseu Diethylpropion; Diethylstilbestrol; Diflorasone; Diflunisal; doephedrine; Nisoldipine: Lisuride: Cinalukast; Aripipra Dimenhydrinate; Dimethyl Sulfoxide: Dinoprost Zole; Clodronate; Testolactone; Formoterol: Diazepam; Cef Tromethamine; Dinoprostone; Diphemanil Methylsulfate: dinir: Tranylcypromine: Penicillin G. Mimosine: Diphenidol; Dipivefrin; Dirithromycin; Docetaxel; Dexfenfluramine; Teniposide; Procaine; Phenoxyben Docosanol; Doxacurium Chloride; Doxapram; Doxylamine: Zamine; Altretamine: Pioglitazone; Fulvestrant; Dex Dromostanolone; Droperidol; Dyclonine; Dydrogesterone: tromethorphan; Acarbose; Methylphenidate; Terconazole; Echothiophate Iodide; Econazole; Edrophonium; Eletriptan; Thiopental; Acamprosate; Valrubicin; Pergolide; Busulfan; Emedastine; Enoxacin; Entecavir, Epoprostenol; Eprosartan; Metoclopramide; Bendroflumethiazide; Terazosin; Metipra Erlotinib. Ertapenem; Erythromycin; Esmolol; Estazolam: nolol; Foscarnet; Buprenorphine; Sufentanil; Imipramine; Ethambutol; Ethchlorvynol; Ethinamate; Ethiodol; Ethiona Caffeine; Dexamethasone; Quetiapine; Temazepam, Ergota mide; Ethotoin: Etidronate; Etomidate; Etretinate; mine; Pindolol; Norethindrone; Midazolam; Lamivudine; Fenoldopam; Fenoprofen; Flavoxate: Flumazenil; Flumetha Chlordiazepoxide; Escitalopram; Sulfamethizole; Mirtazap sone Pivalate: Flunisolide; Fluocinolone Acetonide; Fluoci ine; Cetrorelix; Topotecan; Hydroxyzine; Tripelennamine: nonide: Fluorescein; Fluorometholone: Fluoxymesterone: Tacrine; Ethinyl Estradiol; Floxuridine; Pipobroman; Novo Flurandrenolide: Flurazepam; Flutamide: Fomepizole; biocin; Procarbazine; Decamethonium; Valacyclovir; Leuco Fomivirsen; Fosfomycin; Furazolidone; Gadobenate dime vorin; Vardenafil; Progesterone: Isocarboxazid; Cerulenin: glumine; Gadodiamide; Gadopentetate dimeglumine; Gadot Sulfoxone; Nevirapine; Nizatidine: Eplerenone; Vinblastine; eridol; Gadoversetamide; Galsulfase; Ganirelix; Gatifloxa Desoxycorticosterone Pivalate; Bromodiphenhydramine: cin; Gefitinib; Gentian Violet; Glatiramer Acetate; US 2008/0220441 A1 Sep. 11, 2008

Glycopyrrolate: Gonadorelin; Granisetron; Grepafloxacin: Capromab; Omalizumab; Aldesleukin; Natalizumab: Griseofulvin; Guaifenesin; Guanadrel Sulfate; Guanethidine; Denileukin diftitox; Tositumomab: Somatropin recombinant; Guanidine: Halazepam; Halobetasol Propionate; Halopro Bevacizumab; Octreotide acetate; Serum albuminiodonated; gin: Hetacillin: Hexafluorenium Bromide: Hexylcaine: His Rasburicase: Immune globulin; Botulinum Toxin; Interferon tamine Phosphate: Homatropine Methylbromide; Hydrocor beta-1a; Pegfilgrastim; Interferon alfa-2a: Interferon alfa-n1; tamate; Hydrocortisone; Hydroflumethiazide: Palivizumab; Trastuzumab: Follitropin alfa/beta; Pegade Hydromorphone; Hydroxocobalamin: Hydroxypropyl Cellu mase bovine; Serum albumin; Anistreplase; Epoetin alfa: lose; Hydroxystilbamidine Isethionate; Ibutilide Fumarate; Urofollitropin; Insulin recombinant; Enfluvirtide; Arcitumo Icodextrin; Iloprost: Imatinib. Imiquimod; Indapamide; mab: Satumomab Pendetide; Alemtuzumab. Vasopressin; Indecamide: Inulin; Iron Dextran; Isoniazid: Ivermectin; Daptomycin; Desmopressin; Goserelin; Fely pressin; Ketoprofen; Ketorolac. Ketotifen Fumarate; Labetalol; Cetrorelix; fkb-001; timc114; uic-94.017; ca-074: In-(I-3- Lactulose; Latanoprost: Letrozole; Levamisole; Levetirac trans-propylcarbamoyl-oxirane-2-carbonyl)-I-isoleucyl-I- etam; Levocabastine; Levocarnitine; Lindane; Linezolid; proline: 4-5-2-(1-phenyl-ethylamino)-pyrimidin-4-yl)-1- Liothyronine; Lomefloxacin; Loracarbef; Loteprednol Eta methyl-4-(3-trifluoromethylphenyl)-1h-imidazol-2-yl)- bonate; Magnesium Sulfate; Malathion; Mannitol; Masopro piperidine; 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2h col; Mazindol; Mebendazole; Meclofenamate; Medrysone: tetrazol-5-yl)-propenone; 2'-deoxy-adenosine Megestrol; Mepivacaine; Meprobamate; Mercaptopurine; 3'-monophosphate: 4-(5-bromo-2-oxo-2h-indol-3-ylazo)- Meropenem; Mesalamine; Mefformin; Metixene; Methocar benzenesulfonamide; didecyl-dimethyl-ammonium; (1n)-4- bamol; Methyclothiazide; Methylaminolevulinate; Methyl n-butoxyphenylsulfonyl-(2r)-n-hydroxycarboxamido-(4s)- dopa; Metolazone; Metyrapone: Metyrosine: Mezlocillin; methanesulfonylamino-pyrrolidine; 7,8-dihydroxy-1- Micafungin; Miconazole; Midodrine: Miglitol; Miglustat; methoxy-3-methyl-10-oxo-4,10-dihydro-1h.3h-pyrano.4.3- Mivacurium; Moexipril; Monobenzone: Moricizine: bchromene-9-carboxylic acid; mevastatin: 2-(2-oxo-1,2- Nabilone; Nabumetone; Nafarelin; Nafcillin; Naftifine; Nal dihydro-pyridin-3-yl)-1h-benzoimidazole-5-carboxamidine: buphine; Nalidixic Acid; Naproxen; Natamycin; Nedocro 2-(2-hydroxy-phenyl)-3h-benzoimidazole-5-carboxami mil: Nitisinone; Nitric Oxide: Nitroprusside; Nystatin; Osel dine: 2-(2-hydroxy-5-methoxy-phenyl)-1h-benzoimidazole tamivir Phosphate: Oxacillin: Oxamniquine; Oxandrolone: 5-carboxamidine: 2-(2-hydroxy-phenyl)-1h-indole-5-car Oxazepam. Oxiconazole Nitrate; Oxymetazoline; Pamidr boxamidine; spiro (2,4,6-trinitrobenzene 1,2a-2o'.30'- onate; Paricalcitol; Pemoline: Penicillamine; Pentagastrin; methylene-adenine-triphosphate: 20formyl-hydroxy Pentazocine: Pentobarbital; Pentosan Polysulfate: Perflutren: amino)-ethyl-phosphonic acid; 12-hydroxydodecanoic acid; Perindopril Erbumine: Pimecrolimus: Piroxicam, Podofilox: 6-chloro-2-(2-hydroxy-biphenyl-3-yl)-1 h-indole-5-carboxa Polymyxin B Sulfate; Pralidoxime; Praziquantel; Prednicar midine: 1-(o-carboxy-phenylamino)-1-deoxy-d-ribulose-5- bate; Pregabalin: Propofol; Pyrazinamide: Rabeprazole; phosphate; n-5'-O-phosphono-ribofuranosyl-2-2-hydroxy Ramelteon; Remifentanil; Rifapentine; Rifaximin; Rimanta 2-4-glutamic acid-n-carbonylphenyl-3-2-amino-4- dine: Rimexolone; Rocuronium; Sevelamer; Sotalol; Spar hydroxy-quinazolin-6-yl-propanylamino-acetamide; 1,3- floxacin; Spectinomycin; Spironolactone; Succimer, Sucral dihydroxyacetonephosphate: n-hexadecanoylglycine; fate; Sulindac.; Tazarotene; Telmisartan; Tenofovir, 2-amino-3-5-(amino-carboxy-methyl)-2,3-dihydro-isox Thalidomide: Thiabendazole; Ticlopidine; Tiludronate: aZol-3-ylsulfanyl-propionic acid; tris-hydroxymethyl-me Timidazole; Tioconazole; Tocamide; Tolazamide; Tolimetin; thyl-ammonium: 1-o-o-nitrophenyl-beta-d-galactopyra Trandolapril; Tranexamic Acid; Travoprost: Treprostinil; Tri nose; Sa146; 1-o-p-nitrophenyl-beta-d-galactopyranose; fluridine; Trilostane; Trimethobenzamide; Trovafloxacin; d-galctopyranosyl-1-on; n-(3-(aminomethyl)benzyl)aceta Vancomycin; Verteporfin; Zoledronate; Levosimendan; Tet midine; 4,5-dimethyl-1,2-phenylenediamine; (3-carboxy-2- rahydrobiopterin; Lubiprostone; Dornase alfa (Dnase); (r)-hydroxy-propyl)-trimethyl-ammonium; (2S)-2-(2,4- Alpha-1-proteinase inhibitor; Cyclosporine; Infliximab: dichloro-benzoyl)-(3-trifluoromethyl-benzyl)-amino-3- Muromonab: Coagulation factor VIIa; Daclizumab: phenyl-propionic acid, (2S)-2-(5-benzofuran-2-yl-thiophen Laronidase; Leuprolide; Collagenase; Asparaginase; Oral 2-ylmethyl)-(2,4-dichloro-benzoyl)-amino-3-phenyl interferon alfa: Reteplase; Rituximab: Ribavirin and Alfa propionic acid; 6-In-(1-isopropyl-3,4-dihydro-7- Interferon (Intron A); Oxytocin; Interferon gamma-1b: isoquinolinyl)carbamyl-2-naphthalenecarboxamidine; Menotropins; Tenecteplase; Thyrotropin Alfa; Oprelvekin; 4-3-oxo-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphtha Hyaluronidase; Interferon alfa-n3; Lepirudin; Calcitonin, len-2-yl)-propenyl]-benzoic acid; n-3-4-(3-amino-propyl)- salmon: Imiglucerase; Digibind; Streptokinase; Antihemo piperazin-1-yl)-propyl)-3-nitro-5-(galactopyranosyl)-beta philic Factor: Urokinase; Insulin, porcine; Darbepoetin alfa: benzamide; 5-4-(1-carboxymethyl-2-oxo Sermorelin; Choriogonadotropinalfa, SargramoStim; Grami propylcarbamoyl)-benzylsulfamoyl-2-hydroxy-benzoic cidin D; Alglucerase: Factor IX; Secretin, synthetic; Antithy acid; pantothenyl-aminoethanol-acetate pivalic acid; 1-(4- mocyte globulin; Abciximab; Palifermin; Peginterferon alfa tert-butylcarbamoyl-piperazine-1-carbonyl)-3-(3-guani 2a; Pegvisomant; Insulin Glargine recombinant; Digoxin dino-propyl)-4-oxo-aZetidine-2-carboxylic acid; cetyl-trim Immune Fab; Peginterferon alfa-2b: Adalimumab. Alteplase; ethyl-ammonium; 1,6-diaminohexane; 16 g; 2-phenylamino Abarelix; Etanercept; Becaplermin; OspA lipoprotein; Ale ethanesulfonic acid; 2-amino-5-hydroxy-benzimidazole; facept; Lutropin alfa, Glucagon recombinant; Human Serum benzoylformic acid: 4-chlorobenzoic acid; 3,5-dihydro-5- Albumin; Anakinra, Desmopressin acetate; Interferon alfa methylidene-4h-imidazol-4-on: 4-(4-hydroxy-3-isopropy con-1; Eptifibatide; Follitropin beta; Insulin Lyspro recombi lphenylthio)-2-isopropylphenol; brms 184394; 1-(1-methyl nant; Interferon alfa-2b: Pancrelipase: Drotrecogin alfa, Ibri 4.5-dioxo-pent-2-enylcarbamoyl)-2-phenyl-ethyl-carbamic tumomab: Botulinum toxin type B; Cetuximab: Filgrastim; acid benzyl ester, propionyl coenzymea, (2S)-4-(beta-alany Basiliximab; Efalizumab; Agallsidase beta; Bivalirudin; lamino)-2-aminobutanoic acid: 4-2-(3-nitrobenzoyl) Gemtuzumab ozogamicin; Interferon beta-1b; Pegaspargase; aminolphenoxyphthalic acid: 4-2,4-bis(3-nitrobenzoyl)

US 2008/0220441 A1 Sep. 11, 2008 amate; d-Xylitol; Xylopyranose; cysteine-S-acetamide; 2.5- brompheniramine\dexbrompheniramine; buclizine; budes dimethylpyrimidin-4-amine; 5-ethyl(methyl)amino onide; buprenorphine; bupropion; buspirone; buSulfan; methyl)-2-methyl-5,6-dihydropyrimidin-4-amine; 7,10,13 butenafine; butoconazole; butorphanol; cabergoline; calcife tri(carboxymethyl)-5, 15-dioxo-4,7,10,13,16-pentaaza-1, 19 diol, calcipotriol/calcipotriene; calcitonin human; calcitriol: dithianonadecane; 3-fluorotyrosine: (s)-3-(4-(2-carbazol-9- candesartancilexetil, candicidin; capecitabine; capreomycin; yl-ethoxy)-phenyl)-2-ethoxy-propionic acid; carbachol; carbenicillinindanyl sodium; carboprost, carmus tyrosyladenylate; y-700; 7-hydroxy-2-oxo-chromene-3-car tine; carphenazine; carprofen; carteolol; carvedilol; caspo boxylic acid ethyl ester: Zebularine; p 1-(5'-adenosyl)p5-(5'- fungin, cefaclor, cefazolin, cefepime; cefotaxime; cefoxitin; (3'azido-3'-deoxythymidyl)pentaphosphate; z-ala prolinal; ceftazidime; cefuroxime; celecoxib; cephalexin; cephalogly 3-(acetyl-methyl-amino)-methyl-4-amino-n-methyl-n-(1- cin; cephalothin; cephapirin; cephradine; cerivastatin: ceru methyl-1h-indol-2-ylmethyl)-benzamide: 6-(4-difluo letide; cetirizine; cetrorelix; cevimeline; chenodiol\ursodiol; romethoxy-3-methoxy-phenyl)-2h-pyridazin-3-one; Zn(ii)- chlorambucil; chloramphenicol palmitate; chlordiazepoxide; (20-oxo-protoporphyrin ix): 4-(6-chloro-naphthalene-2- chlorhexidine gluconate; chlorphenesin carbamate; sulfonyl)-piperazin-1-yl)-(3,4,5,6-tetrahydro-2h-14 chlorpheniramine\dexchlorpheniramine; chlortetracycline; bipyridinyl-4-yl)-methanone; 3-(4-bromo-2-fluoro chlorthalidone; cholecalciferol; ciclopirox: cidofovir; cilas benzyl)-7-chloro-2,4-dioxo-3,4-dihydro-2h-quinazolin-1- tatin; cilostaZol, cinacalcet, ciprofloxacin, cisapride; yl)-acetic acid; (3r)-3-(benzyloxy)carbonyl)amino-2- citalopram\escitalopram; cladribine; clavulanate; clemas oXo-4-phenylbutane-1-diazonium, Zinc trihydroxide; tine; clindamycin palmitate; clobetasol propionate; clocor 9alpha-fluorocortisol; protoporphyrin ix containing Zn; tolone pivalate; clofarabine; clopidogrel, cloraZepate; clox Z-pro-prolinal; benzoyl-arginine-alanine-methyl ketone; acillin; clozapine; cobalamin\hydroxocobalamin; colfosceril arecoline; daZOXiben; enalkiren, eniluracil; fotemustine; hex palmitate; colistimethate sodium; colistin; conivaptan; corti obarbital; hirulog; methoxyamphetamine; nalorphine; corelin ovine triflutate; corticotropin; cosyntropin; cyclacil peldesine; phenacetin; phencyclidine, piretanide; Sorbinil; lin; cyclobenzaprine; cyclopentolate; cyclosporine; terlipressin; thiorphan; vanoxerine; Vitamin C; Vitamin B6 cycrimine; cytarabine; dacarbazine; dactinomycin; dalfopris (Pyridoxine); Calcitriol: Vitamin B12: Vitamin D2 (Ergocal tin, dantrolene; dapiprazole; daptomycin; darifenacin; ciferol); Calcidiol; Vitamin A; Vitamin D3 (Cholecalciferol): deferasiroX, delavirdine; demecarium; desirudin; deslano Vitamin B1 (Thiamine); Vitamin B2 (Riboflavin); Adenosine side; desloratadine; desmopressin; desogestrel; desonide; monophosphate; Adenine; L-Alanine: L-Arginine: L-Aspar desoximetaSone; desoxycorticosterone pivalate; dexametha agine; L-Aspartic Acid, Adenosine triphosphate: Cysteine; SO sodium phosphate: dexmedetomidine: Biotin: Choline: Citrulline; Creatine: L-Cystine: Icosapent; dexmethylphenidate\methylphenidate; dexpanthenol; dexra Folic Acid, L-Glutamine: L-Glutamic Acid; Glycine; Glu ZOXane, dextromethorphan polistirex; tathione: L-Histidine: L-Isoleucine; 9-Homolinolenic acid; dextrothyroxine\levothyroxine; dezocine; diatrizoate meglu L-Leucine; a-Linolenic acid; Lipoic Acid, Xanthophyll; mine; dichlorphenamide; dicloxacillin; didanosine; diethyl L-Lysine: L-Methionine; N-Acetyl-D-glucosamine:NADH: propion; diethylstilbestrol; difenoxin; diflorasone diacetate; Nicotinic acid: L-Ornithine; L-Phenylalanine: Pyridoxal P: digoxin; dinoprost tromethamine; dinoprostone; diphen Aspartame; L-Proline; Phosphatidylserine: Pyridoxal; Pyru methanil-methylsulfate/diphemanil; diphenoxylate; dipiv vic acid; Retinoic acid: S-Adenosylmethionine: L-Serine; efrin, docetaxel; dolfetilide; dolasetron; donepezil; dopamine; Succinic acid; Spermine; Tetrahydrofolic acid; L-Threonine: dorzolamide: doxacurium: doxazosin, doxepin, doxercalcif L-Tryptophan: L-Tyrosine: L-Valine; Vitamin E; and Vitamin erol: doxorubicin\epirubicin; dromostanolone propionate; K3. dronabinol; drospirenone; dulloxetine; dutasteride: dyclo 0080. Other chemicals which may be used with the present nine; dydrogesterone; echothiophate; efavirenz; eflornithine; invention include the following, along with any salts and free eletriptan; emedastine; emitricitabine; enalaprilat; enflurane; bases: abacavir, abarelix; acamprosate; acarbose; enfuVirtide; enoxacin; entacapone; entecavir, epinastine; acetophenazine; acetylcysteine; acetyldigitoxin; acitretin: eplerenone; epoprostenol; eprosartan; eptifibatide; erlotinib; acrisorcin; acyclovir, adapalene; adefovir dipivoxil; ertapenem; erythromycinestolate; esmolol; estradiol acetate; adenosine\vidarabine; alatrofloxacin; albendazole; alclom estramustine phosphate; estrone; estropipate; esZopiclone; etaSone; alendronate; alfentanil; alfuZosin; almotriptan; alos ethchlorvynol; ethopropazine; ethotoin: ethylestrenol; etron; alpha-tocopherol\vitamine; alprostadil; ambenonium; ethynodiol diacetate; etidronate; etodolac, etonogestrel; eto amcinonide; amdinocillin; amikacin; aminoglutethimide; poside phosphate, etretinate; exemestane; exenatide; aminolevulinic acid; aminosalicylic acid; amiodarone; eZetimibe; famciclovir; famotidine; felodipine; fexofena amlexanox; amlodipine; amoxapine; amoxicillin; dine; finasteride; flavoxate; floxuridine; fluconazole; amphetamine\dextroamphetamine; amplicillin; amprenavir, fludeoxyglucose f-18; flumazenil; flumethasone pivalate: aminone\inaminone; anagrelide; anastroZole; anidulafungin; flunisolide; fluocinolone acetonide; fluocinonide; fluo anileridine; anisindione; apomorphine: apraclonidine; rometholone acetate; fluoxymesterone; fluphenazine enan aprepitant; arbutamine; argatroban; aripiprazole; atazanavir, thate; fluprednisolone; flurandrenolide; flurbiprofen; fluta atomoxetine; atorvastatin; atracurium\cisatracurium; aurano mide; fluvastatin: fluvoxamine; fondaparinux; formoterol; fin; avobenzone; azatadine, azathioprine; azelastine; aziocil fosamprenavir, foscarnet; fosinopril; fosphenyloin, fro lin; aztreonam, bacampicilling baclofen; balsalazide; beclom Vatriptan; fulvestrant; furazolidone; gabapentin; gadoteridol; ethasone; benazepril; benoximate; bentiromide; benzonatate; gallamine triethiodide; ganciclovir Sodium; ganirelix; gati benzquinamide; betamethasone benzoate; floxacing gefitinib, gemcitabine; gemfibrozil; gemifloxacin; betaxolol\levobetaxolol; betazole; bethanechol; bethanidine; gemtuzumab ozogamicing glimepiride; glucagon; glucono bexarotene; bicalutamide: bimatoprost; biperiden; biso lactone; glutethimide; gonadorelin; goserelin; gramicidin; prolol; bitolterol; bivalirudin; bortezomib; bosentan; brety granisetron; grepafloxacin; guanadrel; guanethidine:guanfa lium; brimonidine: brinzolamide: bromfenac; bromocriptine: cine; halcinonide; halobetasol propionate; haloperidol US 2008/0220441 A1 Sep. 11, 2008 36 decanoate; haloperidol lactate; haloprogin; hetacillin; edisilate; promethazine; propiolactone; propiomazine; pro hexafluorenium; hexocyclium; hydrochlorothiazide; hydro poxyphene; propoxyphene napsylate; propylthiouracil; pro cortamate; hydroxyprogesterone caproate; hydroxyStilbami tirelin; protriptyline; pseudoephedrine; pyrvinium pamoate; dine; hydroxy Zine pamoate; ibandronic-acid\ibandronate; quetiapine; quinapril, quinestrol; quinupristin; rabeprazole; ibuprofen lysine; ibutilide; icodextrin; idarubicin; idoxuri raloxifene; ramelteon; ramipril; ranolazine; rapacuronium; dine; ifosfamide; iloprost; imatinib, imipenem; imipramine remifentanil; repaglinide; rescinnamine; rifapentine; rifaxi pamoate; imiquimod; indinavir, indocyanine green; ioben min, riluzole; rimantadine, rimexolone; risedronate; risperi guane; iocetamic acid; iodamide meglumine; iodipamide done; ritodrine; ritonavir, rivastigmine; rizatriptan; rocuro meglumine; iodixanol; iodoxamate meglumine; iofetamine; nium; rofecoxib; ropinirole; rosiglitaZone; rosuvastatin: iohexyl, iopamidol; iophendylate; iopromide; iothalamate salmeterol Xinafoate, saquinavir, Saralasin; secretin; sel diagnostic; iotrolan; ioVersol, ioxaglate meglumine; ioxilan; egiline; selenomethionine; seractide; sermorelin; Sertacona ipodate; irbesartan; irinotecan; isocarboxazid; isoetharine; Zole; sertraline; sevoflurane; sibutramine; sildenafil citrate; isoflurane; isosorbide dinitrate; isosulfan blue; isradipine; simvastatin; sincalide; Sirolimus; Solifenacin; Sorafenib; ivermectin; ketotifen; labetalol; lamivudine; lamotrigine; Sotalol, spirapril; Stanozolol, stavudine, Streptomycin Sulfate; latanoprost; leflunomide; lenalidomide; lepirudin; letrozole; streptozocin, Sufentanil; Sulbactam, Sulfacytine; Sulfamera leuprolide; levacetylmethadol hydrochloride\levomethadyl Zine; sulfameter, Sulfamethazine; Sulfisoxazole acetyl: acetate; levallorphan; levamisole; levetiracetam; Sumatriptan; Sunitinib. Supprelin/histrelin; Suprofen; tacroli levobunolol; levocabastine; levocarnitine; levomepromazine; mus; tadalafil; tamoxifen, tamsulosin; tannic acid; tazaro levonorgestrel\norgestrel; liothyronine\liotrix; lisinopril; tene; taZobactam, tegaserod; telmisartan; temozolomide; lithium; lodoxamide; lomustine; lopinavir, loracarbef losar teniposide; tenofovir disoproxil; terazosin; terbinafine; teri tan; loteprednol etabonate; lovastatin; loxapine; lubipros paratide; testolactone; testosterone; tetrahydrozoline; thali tone; Iypressin\vasopressin tannate; mazindol; mecamy domide; thiethylperazine; thioguanine; thiopental; thiothix lamine; meclocycline Sulfosalicylate; medry Sone; megestrol ene; thonzonium; tiagabine; ticarcillin; tigecycline; acetate; meglumine metrizoate; meloxicam, melphalan; mep tiludronate; timolol; tinidazole; tioconazole; tiotropium; eridine; mephentermine; mephenyloin, meprednisone; mer tipranavir; tirofiban; tizanidine; tobramycin; tolcapone; captopurine; meropenem; mesna; mesoridazine; metaxalone; tolterodine; topiramate; toremifene; torsemide; trandolapril; methacycline; methanthelinium\methantheline; methaZola tranylcypromine; travoprost; treprostinil; mide; methdilazine; methenamine hippurate; methicillin; tretinoin\alitretinoin\isotretinoin, triamcinolone; triclofos; methimazole; methixene; methohexital; methoxamine: tridihexethyl; triflupromazine; trifluridine: trilostane; tri methoXSalen; methSuximide; methylaminolevulinate; meth methaphan camsylate; trimethobenzamide; trimipramine; tri yldopate; methylergonovine; methylprednisolone acetate; oXSalen; triptorelin pamoate; troglitaZone; tropicamide; tro methyprylon; methysergide; metipranolol; metocurine; spium; trovafloxacin; tubocurarine; tyloxapol; tyropanoate; metolaZone; metrizoate\metrizoic acid; metronidazole; undecoylium; unoprostone isopropyl; Valacyclovir, Valde metyrapone; metyrosine; meZiocillin; micafungin; mido coxib; Valganciclovir, Valproate\valproic acid\divalproex; drine; mifepristone; miglitol; miglustat; milrinone; minoxi valrubicin; Valsartan; Vardenafil; vecuronium; Venlafaxine; dil; mirtazapine; misoprostol; mitotane; mitoxantrone; miva Verapamil: verteporfin; Vinorelbine; viomycin; vitamin a curium: moexipril; molindone; mometasone furoate; palmitate; Voriconazole; Zaleplon; Zanamivir, Ziconotide; montelukast, moricizine; moxalactam; moxifloxacin; mupi Zidovudine; Zileuton, Ziprasidone; Zoledronic acid; Zolmi rocin, nabilone; nafarelin, naftifine; nalbuphine; nalmefene; triptan; Zolpidem; Zonisamide: 1-alpha-24-dihydroxycole naloxone; naltrexone; naratriptan; natamycin; nateglinide; calciferol; 2',3'-dideoxythymidine:5-hydroxyrofecoxib; ace nedocromil; nefazodone; nelarabine; nelfinavir, neomycin; camide-hydrochloride; aceclidine; aceclofenac; aceglatone; nepafenac; nesiritide; netilmicin; nevirapine; nicardipine; acenocoumarol; acepromazine-maleate; acetaminosalol; niclosamide; nifedipine; nilutamide; nimodipine; nisol acetiamine; acetosulfone sodium; acetoxolone; acetylcar dipine; nitaZoxanide; initisinone; nitrofurantoin: nitrofura nitine; acetyldigoxin-beta; acetyldihydrocodeine; acetylstro Zone; nitroglycerin; nizatidine; norelgestromin; norethin phanthidin; acetylsulfamethoxypyrazine; acipimox; acivicin; drone acetate; norethynodrel; norgestimate; nystatin: aclarubicin; ademetionine-disulfate-ditosilate; adenine octinoxate; octreotide: olanzapine; olmesartan medoxomil: hydrochloride; adrafinil; afloqualone; ag-81; ajmalicine; olopatadine; omega-3-acid ethyl esters; omeprazolefesome aklomide; alacepril; alafosfalin; alanosine; alaproclate; prazole; ondansetron; orlistat; orphenadrine citrate; oselta alclofenac; alcloxa: alcuronium-chloride; aldesulfone; mivir; oxacillin, oxamniquine; Oxandrolone; oxaprozin, aldioxa, alfacalcidol; alfadolone-acetate; alfaprostol; alfaxa oXcarbazepine; oxiconazole; OXtriphylline; palonosetron; lone; algestone-acetophenide; alibendol; alinidine; alliza pamidronate; pancuronium; pantoprazole; pantothenic acid; pride; alloclamide; alloyohimbine; allylestrenol; alminopro paramethadione; paramethasone acetate; pargyline; parical fen; almitrine; aloin; alpha-acetyldigoxin; alphaprodine citol; paroxetine; pegaptanib; pemetrexed; pemirolast; penb hydrochloride; alprenolol-benzoate; alrestatin-Sodium; utolol; penciclovir, penicilling procaine; pentagastrin; pen alsactide; aluminum-clofibrate; alverine-citrate; ambicromil: tamidine; pentazocine; pentetreotide; pentolinium; ambucetamide; ambuside; ambutonium-bromide; amdinocil pentostatin: pergolide; perindopril; permethrin; perphena lin-pivoxil, amezinium-metilsulfate; amfenac; amfetaminil; Zine; phensuximide; phentolamine; phenyl aminosalicylate; amifloxacin; amineptine; a minorex, aminothiazoline cam phenylbutaZone; pimecrolimus; pinacidil; pindolol; pioglita phorate; amiprilose-hydrochloride; amisulpride; amitrip Zone; pipecuronium; piperacetazine; piperazine; pipobro tyline embonate; ammonium peroxydisulfate; amorolfine man; pirbuterol, piroXicam, plicamycin; polyestradiol phos hydrochloride; amoSulalol hydrochloride; amphomycin; phate; polymyxin b; porfimer, povidone-iodine; amprolium; amylmetacresol; androsterone; anetholtrithion; pramipexole; pramlintide; pravastatin; prednicarbate; pred angiotensin-2; angiotensin-amide; antrafenine; apalcillin; nisolone acetate; pregabalin; procarbazine; prochlorperazine apaZone: aprindine-hydrochloride; arabinosyluracil-triphos US 2008/0220441 A1 Sep. 11, 2008 37 phate; arbaprostil, argipressin, armodafinilvmodafinil; aroti clovoxamine; cloxacillin benzathine; cobamamide; cocar nolol, arsphenamine; aspoxicillin; atosiban; atromepine; boxylase magnesium; colestyramine hydrochloride; colext avoparcin; azamethonium-bromide; azanidazole; azaperone; ran; colimycin; colistin Sulfate; colistin-b; congo-red; conor aZapetine-phosphate; azaribine; azauridine, azidamfenicol; phone-hydrochloride; cortivazol; cotamine-chloride; azidocillin; azolimine; aZosemide; bacitracin; bambermycin; coumazoline; coumetarol; creatinolfosfate; croconazole bambuterol-hydrochloride; bamethan; bamifylline-hydro hydrochloride; cropropamide; cyamemazine; cyclandelate; chloride; bamipine; barbetonium iodide; barbexaclone: cyclazocine; cycloartenol-ferulate; cyclobendazole; cyclofe befunolol; befuraline hydrochloride; bekanamycin; bemetiz nil; cycloguanil-pamoate; cyclopentamine-hydrochloride; ide; benapry Zine; bencyclane; bendaZac; benethamine-peni cyclopenthiazide; cyclotiamine; cynarine; cyprodenate; cillin; benfluorex; benfotiamine; benfurodil-hemisuccinate; cyproterone; cyproterone-acetate; cytochalasine-d; cytosine; benorilate; benoxaprofen; benperidol; benproperine danitracen; deanol-aceglumate; deanol-phosphate; debriso embonate; benzalamide; benzaldehyde; benzarone; benzilo quin; decoquinate; deflazacort, dehydroemetime; delapril nium-bromide; benziodarone; benznidazole; benzoctamine; hydrochloride; delmadinone-acetate; demegestone; demex benzopiperylone; benzquercin; benzydamine Salicylate; ben iptiline; demoxytocin, denatonium-benzoate; deoxyglucose: Zylhydrochlorothiazide; bergapten; betamipron; bevantolol; deptropine-citrate; desaspidin; detorubicin; dexecadotril; bevonium-metilsulfate; bezitramide; bibrocathol; bicloty dexetozoline; dexlofexidine; dextranomer; dextrofemine; mol; bietaserpine; bifemelane hydrochloride; binifibrate; dextromoramide; diacerein; diacetolol-hydrochloride: biphenamine-hydrochloride; bisantrene; bisbentiamine; bis diacetylmorphine-hydrochloride; diamfenetide; dianhydro butitiamine; bisdequalinium diacetate; bisorcic, bisoxatin galactitol; diaveridine: dibekacin: dibenzepin; dibenzoyl-dis acetate; bm-23014; bolasterone; boldenome-undecylenate: ulfide; dibrompropamidine: dibromsalan: dibunate-sodium; bornaprine; brivudine: bromhexine; bromperidol-decanoate: dichloralphenazone; dichlorisone-acetate; dichlorodifluo bronopol; broparestrol; brotianide; broxaldine; broxuridine: romethane; dichlorotetrafluoroethane; diclofenamide bucindolol; buclosamide; bucloxic-acid; bucolome; bufe sodium; diclofensine; dicolinium-iodide; dieldrin; diethyl tolol; bufotenine; bufrolin; bufuralol; bumadizone; bunami phthalate; diethyltoluamide; difemerine-hydrochloride; dife dine; bunazosin hydrochloride; bunitrolol; bupranolol; namizole; difenpiramide; difetarsone; diflucortolone-valer buquineran; buserelin; buserelin-acetate; butalamine; ate; difluprednate; diftalone; dihexyverine-hydrochloride: butamirate; buthiazide; butibufen; butikacin; butofilolol; dihydralazine; dihydroergocryptine-beta mesilate; dihydro butopiprine; butriptyline; butropium-bromide; buzepide-me tachysterol; dihydroxydibutylether; diisopromine; dilazep: thiodide; cadralazine; cafaminol; caffeine sodium benzoate: diloxanide; dimecrotic-acid; dimefline-hydrochloride: camo.stat mesilate; camylofin, canrenoate-potassium; can dimenorfan; dimethindene maleate; dimethisterone; dim renone; canthaxanthin; capobenic-acid; captodiame-hydro ethylacetamide; dimethyl-phthalate; dimethyltryptamine: chloride; carazolol, carbadox; carbazochrome; carbimazole; dimetofrine; dimetridazole; dimoxyline phosphate; dini carbinoxamine-tannate; carbomer; carboprost-methyl; car profylline; dioxation; dioxybenzone; dipenine-bromide; boduone; carbutamide; carbuterol-hydrochloride; carglumic diphenadione; diphenan; diphenhydramine acefylline; diphe acid; camidazole; caroverine; carpipramine; carubicin; caru nylthiocarbazone; dipipanone-hydrochloride; diprenorphine; monam-Sodium; celiprolol-hydrochloride; cephacetrile dipyrocetyl; disodium adenosine-triphosphate; disulfamide; Sodium; cephaloridine, cethexonium-chloride; cetiedil; ditazole; dithranol-triacetate; dixyrazine; dodicin; domiodol; cetiedil citrate; cetostearyl-alcohol; cetotiamine; cetraxate domperidone; dopexamine, doxantrazole; doXpicomine-hy hydrochloride; cetylpyridinium-chloride; chloral-betaine; drochloride; dropropizine; drostanolone\dromoStanolone; chloramine-b; chlorbenzoxamine; chlorcyclizine; chlorhexa drotaverine; drotebanol; echothiopate-iodide; edoxudine: dol; chlormadinone-acetate; chlormethiazole; chlormethine efaproxiral; efloxate, elcatonin; eledoisin; elizabethin; ellip n-oxide hydrochloride; chlormidazole; chloroxylenol; tinium-acetate; embramine; emepronium-carrageenate; chloroxymorphamine; chlorozotocin, chiorphenoxamine endralazine-mesylate; endrysone; enilconazole; enoXimone; embonate; chlorproethazine-hydrochloride; chlorpromazine enprostil; enviomycin; enviroxime; eperisone-hydrochlo embonate; chlorpyrifos, chlorquinaldol; chlorthenoxazine; ride; epicillin; epiestriol; epimestrol; epithiazide; epi cholesterol: cholinemagnesium trisalicylate; chromocarb; tioStanol; epomediol, eprazinone; eproZinol; eptazocine; chromonar, chrysarobin; cianidanol: ciclaZindol; erythrityl-tetranitrate; erythromycin-propionate; erythromy ciclesonide; cicletanine: ciclonicate; ciclosidomine; ciclox cin-Succinate, erythrosine; eseridine; etamiphyllin camsilate; ilic-acid; cilastatin, n-acetyl; cilaZapril; cilobamine-mesy etebenecid; eterobarb; etersalate; ethadione; ethaverine; ethi late; cinametic-acid; cinchophen; cinepazet, cinepazide; cin azide; ethopabate; ethyl-biscoumacetate; ethyl-icosapentate; metacin; cinoxate, cinpropazide maleate; ciprofibrate; ethyl-loflazepate; ethyl-Orthoformate; ethynodiol; etifelm ciprostene-calcium; ciramadol-hydrochloride; citicoline ine; etifoxine; etiroXate: etodroxizine; etofamide: etofe sodium; clebopride; clefamide; clemizole sulfate; clen namate; etofibrate; etoglucid: etoperidone-hydrochloride; buterol; clidanac; clinofibrate; clioxanide; clobazam; cloben etoricoxib: etosalamide; exalamide; exifone; exiproben; Zorex; clobetasol; clobetasone-butyrate; clobutinol: exisulind; fampiridine; famprofaZone; faZadinium-bromide; clobuZarit; clocanfamide; clocapramine; clocinizine; clo febantel; febuprol; feclobuzone; fedrilate; fely pressin; fenaf dronic acid; clofarabine-triphosphate; clofenamide; clofexa tic-acid; femalamide; femalcomine; fenbendazole; fen mide; clofibrate pyridoxine; clofibride; clofilium-phosphate: butrazate; fencamfamin; fencibutirol; fenclofenac; fenclo clofoctol; cloforex; clometacin; clomethiazole edisilate: nine; fenclozic-acid; fendosal; fenfluramine hydrochloride; clometocillin; clomocycline; clonixin; clopamide; clo fenitrothion; fenmetozole; fenoterol; fenoverine; fenoxazo penthixol-decanoate; cloperastine fendizoate; clopirac, clo line-hydrochloride; fenozolone; fenpentadiol; femproporex: prednol; cloprostenol-sodium; cloranolol; clorexolone; clor fenprostalene; fenduizone; fenretinide; fenspiride; fenthion; giline; cloridarol; clorindione; clorophene; clorprenaline fentiazac, fenticonazole; fentonium-bromide; feprazone; hydrochloride; clortermine; clostebol-acetate; clothiapine; fezatione: fibracillin; flavodic-acid; floctafenine; floranty US 2008/0220441 A1 Sep. 11, 2008

rone; floseduinan; fluianisone; fluazacort; flucloronide; flu msalan; metadoxine; metahexanamide; metallibure zinc: darabine; fludrocortisone; flufenamate-decanoate; fluindi metapramine; meteneprost, metenolone-enanthate; meter one; flumedroxone-acetate; flumequine; flumeridone; goline; metescufylline; mefformin embonate; methallenes flumethiazide; flunixin-meglumine; flunoxaprofen; fluocor tril; methaniazide; methenolone-acetate; methoprene; meth tin-butyl; fluocortolone; fluorescein-dilaurate; fluoresone; oserpidine; methoxyphenamine; methylergometrine; fluotracen; flupamesone; flupentiXol; flupentixol-decanoate; methylthiouracil; metiazinic-acid; metindizate; metioprim; fluperolone-acetate; flupirtine; fluprednidene-acetate; flu metopimazine; mevastatin; mianserin; mibefradil dihydro prostenol-sodium; fluorothyl; fluspirilene; fluticasone propi chloride; mibolerone: mikamycin; milnacipran; miloxacin; onate; flutroline; fominoben; fonazine-mesylate; forme misonidazole; mizolastine; mocimycin; moclobemide; bolone; formestane; formocortal; formosulfathiazole; mofebutaZone; molsidomine; moperone; mopidamol; mor fosfosal; furapromidium; furonazide; fursultiamine; fusaric antel-tartrate; moraZone; morclofone; morinamide; morni acid, gabexate mesilate; gabob; gallopamil; gamolenic-acid; flumate; motretinide; moXaverine; moxestrol; moxonidine; ganglioside; gefarnate, gemeprost, gepefrine; gepirone-hy muZolimine; naboctate-hydrochloride; nadide; nadoxolol; drochloride; gestodene; gestrinone; gitaloxin; gitoformate; nafarelin; nafronyl: naftalofos; naftaZone; nalorphine; nan glaucine phosphate; glibornuride; gliflumide; gliquidone; drolone-cyclohexylpropionate; nebivolol; nequinate; neu glisentide; glisolamide; glisoxepide; glucametacin; glucosul tral-red; niaprazine; nicametate, nicarbazin; nicergoline; nic fone; glucuronamide; glutathione; glybuzole; glyclopyra eritrol; niclofolan; nicoclonate; nicofibrate; nicofuranose; mide; glyconiazide; glycyclamide; glymidine-Sodium; nicofurate; nicorandil; nifemalol; nifuratel; nifurfoline; gramicidin-S, guabenXan; guacetisal; guaiacol-phenylac nifuroxazide; nifursol; nifurtimox; nifurtoinol; nifurzide; etate; guaiapate; guaietolin, gualenate-sodium; guamecy nikometamide; nilvadipine; nimeSulide; nimorazole; nimus cline; guanacline-Sulfate; guanaZodine Sulfate; guanoclor tine: niridazole; nisin; nithiamide; nitrefazole; nitrendipine; Sulfate; guanoxabenz, guanoxan; halofenate; halofluginone; nitroscanate; nitrovin; nitroXinil; nomegestrol-acetate; halometaSone; halopredone; halopredone-acetate; haloxon; nomifensine; nonivamide; norbormide; nordefrin-hydrochlo hematoporphyrin, hepronicate; hetacillin-potassium; ride; norethandrolone; norethisterone-enanthate; norg hexachloroethane; hexacyprone; hexamethonium-tartrate; estrienone; noscapine; nosiheptide; noxiptiline; octafonium hexamidine; hexapropymate; hexestrol-dipropionate; hexeti chloride; octanoic-acid; Octotiamine; octoxynol-9, dine; hexobendine; hexoprenaline; histapyrrodine; oleandomycin-phosphate; omapatrilat; ondaScora; homidium-bromide; homofenazine; hopantenate calcium; opipramol hydrochloride; ornidazole; ornipressin, oxab hyaluronate-sodium; hycanthone; hydrastine-hydrochloride: olone-cipionate; oxaflozane; oxametacin; oxantel-pamoate: hydrobentizide, hydroxydione-sodium-succinate; hydrox oxapium-iodide; oxatomide; oxendolone; oxetorone; yestrone-diacetate; hydroxyphenamate; hypoglycin-a; ibac oxfendazole; Oxfenicine; oxibendazole; oxidopamine; OXini itabine; ibopamine; ibudilast; ibufenac; ibuproxam: ibuterol: acate olamine; oxiperomide; oxiracetam; oxitriptan; oxybro idebenone; idrocilamide; ifenprodil; imafen-hydrochloride: monaftoic-acid; oxychlorosene; oxyclozanide; oxyfedrine; imaZodan; imcarbofos; imidapril; imidocarb; imipraminox oxymesterone; oxypendyl, oxypertine; padimate-a; padi ide; imolamine; impromidine-hydrochloride; indeloxazine; mate-o; palmidrol; pancreozymin, panipenem; papaveroline; indenolol; indobufen, indoramin; inosine-pranobeX; ioben parapenzolate-bromide; pararosaniline-pamoate; parathiaz Zamate; iocarmic acid; iodamide; iodopyracet (i125); iodot ine teoclate; parecoxib; pargeverine; parsalmide; pas-hy hiouracil; iodothymol; iodoxamic-acid; iotasul; ipriflavone; drazide; pasiniazid; pecilocin, pefloxacin; penfluridol; pen iproclozide, ipronidazole; isoaminile; isobromindione; gitoxin; penimepicycline; pentaerythritol-tetranitrate; isobutiacilate; isoconazole; isoflupredone-acetate; isoleu pentagestrone-acetate; pentetate meglumine; penthienate; cine; isoly Sergide, isomalt, isonixin; isospaglumate magne pentisomicin; pentrinitrol; peplomycin-sulfate; pepstatin: sium; isosulphan-blue; josamycin-propionate; kainic-acid; perazine; perhexyline phosphate; periciazine embonate; per kawain; kebuZone; keracyanin; ketanserin; ketobemidone; lapine; peruvoside; pheneticillin; phenglutarimide: phen kitasamycin; lachesine-chloride; lacidipine; lactalfate; lacti probamate; phenyltoloxamine citrate; phenyramidol; pholco tol; laetrile; lanatoside-c; lasalocid-Sodium; laurolinium dine, phthalofyne; phytate-persodium; picloxydine; acetate; lawsone; lercanidipine; lergotrile-mesylate; leto picotamide, pifamine; pimethixene; pinaverium-bromide; Steine; leucocianidol; levomepromazine embonate; levo pipamazine; pipamperone; pipazethate; pipebuZone; piper moprolol; levopropoxyphene dibudinate; levopropylcillin; oxan; pipethanate-ethobromide; pipotiazine-palmitate; levopropylhexedrine; levoprotiline; levosimendan; lidofla pipoxolan-hydrochloride; pipratecol; piprinhydrinate; pipro zine; lisuride; lobeline; lodoxamide, desethyl: lofentanil Zolin; pirarubicin; piraZolac, pirenoXine;piremperone; piren oxalate; lofepramine; loflucarban; lonazolac, lonidamine; Zepine; piretanide; piribedil: pirifibrate; pirimiphos-ethyl: lorajmine-hydrochloride; lornoxicam, lucanthone; lupros pirimiphos-methyl; pirisudanol; piritramide; pirlindole; pir tiol; lymecycline; lynestrenol; magaldrate; magnesium glu menol-hydrochloride; piroheptine; piromidic-acid; piroxi ceptate; malachite-green-oxalate; mandelic acid; mannomus mone: pirozadil; pirprofen; pivampicillin; pivoefalexin tine; maZaticol; mebanazine; mebeverine embonate; hydrochloride: pizotyline; plafibride; plaunotol; poldine: mebhydrolin; mebhydrolin napadisilate; mebolazine; mebu polymyxin; polynoxylin; polyoxyethylene-cetyl-ether; tizide, mecobalamin; mecrifurone; medifoxamine; medroge polyphloroglucinol-phosphate; ponalrestat; potassium poly stone; medroxalol hydrochloride; medroxyprogesterone; styrene-Sulfonate; practolol; prajmalium bitartrate; pramiver medrylamine; mefenidramium-metilsulfate; mefenorex; ine; pranoprofen; pranosal; prednazoline; prednimustine; mefruside; meglutol; melanostatin: melarsonyl-potassium; prednisolamate; prednylidene; prednylidene-diethylami melitracen; melperone; memotine-hydrochloride; menate noacetate; prenalterol-hydrochloride; prenoxdiazine; trenone; mepartricin-lauryl-sulfate Sodium; mephenoxalone; prenoxdiazine hibenzate; prenylamine; pristinamycin; pro mepindolol; mepitioStane; mepixanox; meproscillarin; caterol; procodazole; profenamine hibenzate; progabide; meptazinol; mesterolone; mesulergine; mesulfen, metabro proglumetacin; proglumide; promazine embonate; pro US 2008/0220441 A1 Sep. 11, 2008 39 mazine-hydrochloride; promegestone; promestriene; propac triclobisonium-chloride; triclocarban; triethylenemelamine; etamol; propallylonal; propamidine; propanidid; propatyl trifenmorph; trifluperidol; triflusal; triiodostearate-ethyl; tri nitrate; propiram; propiverine hydrochloride; propizepine; maZosin; trimebutine; trimetazidine; trimethidinium-metho propyleneglycol-monostearate; propyl-gallate; propy sulfate; trimetrexate; trimoprostil; tripamide; tritiozine; trito phenaZone; propyromazine-bromide; produaZone; pro qualine; trofosfamide; troInitrate-phosphate; tromantadine; renoate-potassium; proscillaridin; prostalene; prothipendyl; tropatepine; tropenZiline-bromide; tropisetron hydrochlo protionamide; protizinic-acid; protoveratrine-b; proxazole; ride; trospectomycin; troXerutin; troXipide; tulobuterol; proXicromil, prozapine; psilocybine; puromycin; pyrantel; tybamate; tymazoline; tyrothricin, ubiquinone; udpg, ufe pyrantel-pamoate; pyricarbate; pyritidium; pyritinol; pyrov namate; undecenoate calcium; unitiol; urapidil; uraZamide; alerone-hydrochloride; pyrrobutamine-phosphate; pyrrolni valnoctamide: valproate-pivoxil; Valspodar, vasopressin; vel trin; quinagolide; quinbolone; quinestradol; quingestanol-ac nacrine; veralipride; Vesnarinone; Vetrabutine; vigabatrin; etate; quinidine Sulfate; quinocide; quinoline-yellow: Viloxazine-hydrochloride; Viminol; vinburnine; Vincamine; quinupramine; quinuronium-sulfate; rafoxanide; raltitrexed: Vincamine-teprosilate; Vindesine; Vinpocetine; vinylbital; ramoplanin; ranimustine; rasagiline mesilate; reboxetine; Vinzolidine Sulfate; Viprostol; vicquidil; virginiamycin; Visna remoxipride; reproterol: rifamide: rimazolium-metilsulfate; dine: Xamoterol-fumarate; Xanoxic-acid; Xantofyl-palmitate; rimiterol: rioprostil; ritanserin; rociverine; rolipram, ronida Xibornol; Xipamide; Xylazine; Zaprinast; Zimeldine; Zinosta Zole; rosaprostol; rosaramicin; roSoxacin; roXarsone; roXati tin, Zipeprol; Zolimidine; Zomepirac, Zorubicin; Zotepine; dine acetate; roXithromycin; ruscogenin; Safrazine; salicy Zucapsaicin; and Zuclopenthixol-acetate. late-ethyl; salmefamol, sapropterin; sc-44463; secnidazole; I0081 Chemicals that are especially preferable to be used sefavirenz, Semustine; Sennoside; Sennoside-a; serotonin; with the present invention include the following chemicals sertindole; simfibrate; sizofuran; sobrerol; sodium cefu and their salts and free bases: abarelix, abciximab, acampro Zonam, Sodium estriol-succinate; sodium flomoxef sodium sate, acetazolamide, acetohexamide, acetophenazine, acetri picosulfate; sodium polymetaphosphate; sodium predniso Zoate, acetylcysteine, adefovir dipivoxil, alatrofloxacin, lone-meta-sulfobenzoate; sodium warfarin; Sodium-bensul albendazole, alclometaSone, alendronate, almotriptan, alpra dazate; sodium-loxoprofen; Sodium-OZagrel; Solasulfone; Zolam, ambenonium, amifostine, amiloride, amiodarone, Somatostatin: Sorbinil; Sorbitan-monolaurate; spaglumic amlodipine, amlodipine, amodiaquine, amoxapine, amoxicil acid; Sparteine amp; Sparteine theophylline; spiclomazine; lin, amplicillin, amprenavir, anagrelide, anakinra, apracloni spiperone; spiramycin adipate; stallimycin; Stepronin; stib dine, aprepitant, ardeparin, argatroban, aripiprazole, artic ocaptate; stilbophen; stilbazium iodide; strophanthin-h; suc aine, atorvastatin, atovaquone, auranofin, azathioprine, cinimide; succinylsulfathiazole bismuth; sulbenicillin; sulbu aZelastine, aziocillin, aztreonam, bacampicillin, bacitracin, tiamine; Sulfadicramide; Sulfaguanole; baclofen, beclomethasone, bendroflumethiazide, benzthiaz Sulfamethoxypyridazine-acetyl, sulfametrole; sulfa ide, betamethasone, bicalutamide, bismuth Subsalicylate, monomethoxine, Sulfanitran; Sulfaperin; Sulfaproxyline; Sul bleomycin, bosentan, bretylium, brimonidine, brinzolamide, faquinoxaline, Sulfarsphenamine; Sulfazamet, Sulfuram; Suli bromfenac, bromocriptine, bromodiphenhydramine, bro satin: Sulmazole, Sulpiride adamantanecarboxylate; mpheniramine, buclizine, bumetanide, bupropion, buSulfan, Sulprostone; Sulthiame; Sultopride; Sultroponium; Sunset-yel butalbital, butoconazole, capecitabine, capreomycin, capto low; SuXethonium-chloride; SuXibuZone, Syrosingopine; pril, carbenicillin, carbenicillin indanyl, carbinoxamine, car talampicillin-hydrochloride; taleranol; tamitinol; tartrazine; boplatin, carmustine, carphenazine, carprofen, cefaclor, taxol; teclothiazide, teclozan, tedelparin, tefazoline; teico cefadroxil, cefamandole, cefazolin, cefdinir, cefditoren, planin; temafloxacin; temocillin; temoporfin, tenamfe cefepime, cefixime, cefimenoxime, cefimetazole, cefonicid, tamine; tenidap; tenitramine; tenonitrozole; tenoxicam, cefoperaZone, ceforanide, cefotaxime, cefotetan, cefotiam, teprenone; teprotide; terizidone; terlipressin; terlipressin cefoxitin, ce?piramide, cefpodoxime proxetil, cefprozil, acetate; terodiline-hydrochloride; tertatolol; tetrabenazine: ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, tetradecylsulfate-sodium; tetrahydrozoline hydrochloride; cefuroxime, cefuroxime axetil, celecoxib, cephalexin, cepha tetramethrin, tetrydamine; tezosentan; thebacon; theobro loglycin, cephalothin, cephapirin, cephradine, cerivastatin, mine-sodium-acetate; theofibrate; theophylline-acetate-so cetirizine, cetrorelix, cevimeline, chlophedianol, chloram dium; thiambutosine; thiamine-propyl-disulfide; thiam bucil, chloramphenicol, chlordiazepoxide, chlorhexidine, phenicol-glycinate hydrochloride; thiamphenicol-palmitate; chlormeZanone, chloroprocaine, chloroquine, chlorothiaz thiamylal-Sodium; thiazinamium; thiazolsulfone; thibenza ide, chlorotrianisene, chloroxine, chlorphenesin, chlorphe Zoline; thiocolchicoside; thiophanate; thiopropazate; thiou niramine, chlorphentermine, chlorpromazine, chlorpropam racil; thymalfasin; thymopentin; tiamenidine; tiamulin-fu ide, chlorprothixene, chlortetracycline, chlorthalidone, marate; tianeptine; tiapamil-hydrochloride; tiapride; chlorZoxaZone, chromium picolinate, chromium salts, cilas tiaprofenic acid; tiaramide-hydrochloride; tibeZonium-io tatin, cimetidine, cinacalcet, ciprofloxacin, cisapride, cispl dide; tibolone; ticrynafen; tidiacic, tiemonium-iodide; tigloi atin, citalopram, cladribine, clemastine, clindamycin, clinda dine; tilidine-hydrochloride; timepidium bromide; timonacic mycin, clindamycin, clioquinol, clobetasol, clocortolone, arginine; tinoridine, tiocarlide; tioclomarol; tioXolone; tipe clofarabine, clofazimine, clofibrate, clomiphene, clomi pidine hibenzate; tiquizium-bromide; tiratricol; tirilazad; pramine, clonazepam, clonidine, clopidogrel, cloraZepate, tiropramide; tiXocortol-pivalate; tocamphyl; tocopherol-al clotrimazole, cloxacillin, clozapine, colestipol, cyclophos pha-nicotinate; tocopheryl-quinone; todralazine; tolciclate; phamide, cyclothiazide, cysteamine, cysteine, dalfopristin, tolmesoxide; tolnaftate; toloconium-metilsulfate; tolonidine; dapsone, delavirdine, demeclocycline, desflurane, deslorata toloxatone; tolperisone; tolpropamine; tolrestat; tonazocine dine, desmopressin, dexamethasone, dexamethasone, dex mesylate; tosactide; tramaZoline; tranilast; trenbolone; tren amethasone, dexbrompheniramine, dexchlorpheniramine, bolone-cyclohexylacetate; trengestone; treosulfan; treto diatrizoate, diazepam, diazoxide, dichlorphenamide, quinol; triacetin; tribenoside; tribromoethanol; tribuZone: diclofenac, dicloxacillin, diethylstilbestrol, diflorasone, US 2008/0220441 A1 Sep. 11, 2008 40 diflunisal, diltiazem, dimenhydrinate, dimercaprol, dimethyl quinethaZone, quinupristin, rabeprazole, raloxifene, raniti sulfoxide, dimyristoyl, disulfiram, dofetilide, dorzolamide, dine, ranitidine bismuth citrate, riluzole, risedronate, risperi droperidol, dulloxetine, dutasteride, echothiophate, econa done, ritonavir, rofecoxib, rose bengal, rosiglitaZone, rosuv Zole, efavirenz, eflornithine, eletriptan, emitricitabine, enflu astatin, rubidium salts, Samarium lexidronam, Selenium rane, enoxacin, eprosartan, eptifibatide, ertapenem, escitalo Sulfide, selenite salts, selenate salts, selenomethionine, Serta pram, esmolol, esomeprazole, estazolam, estramustine, conazole, Sertraline, sevoflurane, Sibutramine, sildenafil, sil eSZopiclone, ethacrynate, ethacrynic acid, ethchlorVynol, ver Sulfadiazine, simethicone-cellulose, Sodium fluoride, ethiodized oil, ethionamide, ethopropazine, ethoXZolamide, Sodium iodide, Sotalol, sparfloxacin, spirapril, spironolac etidronate, etoposide, evans blue, eZetimibe, famotidine, tone, strontium chloride. Succimer, Sucralfate, Sufentanil, Sul felodipine, fenofibrate, fenoldopam, flecamide, floxuridine, conazole, Sulfacetamide, Sulfacytine, Sulfadiazine, Sulfadox fluconazole, flucytosine, fludarabine, fludeoxyglucose, ine, Sulfamerazine, Sulfameter, sulfamethizole, fludrocortisone, flumazenil, flumethasone, flunisolide, fluo Sulfamethoxazole, Sulfanilamide, Sulfaphenazole, Sulfasala cinolone acetonide, fluocinonide, fluorometholone, fluo Zine, Sulfinpyrazone, Sulfisoxazole, Sulfisoxazole acetyl, Sul rometholone, fluorouracil, fluoxetine, fluoxymesterone, foxone, Sulfur, Sulindac, Sumatriptan, Sumatriptan, Suprofen, fluiphenazine, fluiphenazine enanthate, fluiphenazine, flupred tamsulosin, tazarotene, taZobactam, temazepam, teniposide, nisolone, flurandrenolide, flurazepam, flurbiprofen, fluta tenofovir disoproxil, terconazole, thallous chloride, thia mide, fluticaSone, fluvastatin, fluvoxamine, fomivirsen, bendazole, thiamine, thiamylal, thiethylperazine, thiogua fondaparinux, foSamprenavir, foScarnet, fosfomycin nine, thiopental, thioridazine, thiotepa, thiothixene, tiagab tromethamine, fosinopril, froVatriptan, fulvestrant, furo ine, ticarcillin, ticlopidine, tiludronate, timolol, tinidazole, semide, gadobenate, gadodiamide, gadopentetate, gadoteri tinzaparin, tioconazole, tiopronin, tiotropium, tirofiban, tiza dol, gadoversetamide, gallium citrate, gallium salts, ganire nidine, tolaZamide, tolbutamide, topiramate, toremifene, lix, gatifloxacin, gefitinib, gemcitabine, gemifloxacin, torsemide, travoprost, trazodone, triamcinolone, triamcino glimepiride, glipizide, glucagon, glyburide, grepafloxacin, lone acetonide, triamcinolone diacetate, triamcinolone griseofulvin, guanabenz, guanfacine, halazepam, halobeta hexacetonide, triazolam, trichlormethiazide, triclofos, tri Sol, halofantrine, haloperidol, haloprogin, halothane, hep closan, trifluoperazine, triflupromazine, trifluridine, trime arin, hexachlorophene, hydrochlorothiazide, hydrocortisone, prazine, trimethaphan, troglitaZone, trovafloxacin, tyro hydroflumethiazide, hydroxocobalamin, hydroxychloro panoate, uracil mustard, Valdecoxib, valrubicin, Vancomycin, quine, hydroxyzine, ibandronate, ibutilide, idoxuridine, ifos Vardenafil. Voriconazole, Zafirlukast, Ziconotide, Zileuton, famide, imipenem, indapamide, indium and its salts, indium Ziprasidone, Zoledronic acid. The present invention is espe oxyquinoline, indium pentetate, indium, indocyanine green, cially useful when a solution of at least two chemicals is used, indomethacin, iobenguane, iocetamic acid, iodamide, iodipa where the first chemical is selected from the above lists of mide, iodixanol, iodohippurate, iofetamine, iohexyl, iopami chemicals and the second chemical does not have the same dol, iopanoic acid, iopromide, iothalamate, iothalamate, empirical formula as the first chemical. iotrolan, ioVersol, ioxaglate, ioXilan, ipodate, isoflurane, isof I0082 Protein classes that are especially preferable to use luorophate, itraconazole, ketamine, ketoconazole, ketotifen, with the present invention consist of the following list: Cytok lamivudine, lamotrigine, lanSoprazole, leflunomide, levami ines; chemokines; G protein-coupled receptors; Glycosi sole, levocabastine, levofloxacin, levothyroXine, lincomycin, dases; glycosyltransferases; Ion channels: Nuclear receptors; lindane, lineZolid, liothyronine, lodoxamide, lomefloxacin, Phosphodiesterases: Proteases: Protein kinases: Protein lomustine, loperamide, loracarbef, loratadine, lorazepam, phosphatases; Nucleic acids; Transporter proteins; Serotonin losartan, loteprednol, loxapine, mafenide, magnesium salts, receptors; Dopamine receptors; Adrenergic receptors; Hista malathion, mangafodipir, manganese salts, mazindol, mine receptors; Muscarinic receptors; Nucleotide receptors; mechlorethamine, meclizine, meclocycline, meclofenamate, Cannabinoid receptors; Chemokine receptors; Opioid recep mefloquine, meloxicam, melphalan, mercaptopurine, mero tors; Tyrosine kinases; Cytoplasmic serine kinases; cytoplas penem, mersalyl, mesoridazine, methazolamide, methdila mic threonine kinases; Thyroid hormone-like receptors; Zine, methicillin, methimazole, methixene, methotrimepra HNF3-like receptors; and Estrogen-like receptors. Proteins Zine, methoxyflurane, methyclothiazide, metoclopramide, that are especially preferable to use with the present invention metolaZone, metrizamide, mezlocillin, micafungin, micona consist of the following list: 1,3,4,6-Tetrachloro-1,4-Cyclo Zole, midazolam, mitotane, modafinil, mometaSone, mon hexadiene H; 1,3,6,8-Tetrahydroxynaphthalene Reductase: telukast, moxalactam, moxifloxacin, nafcillin, naratriptan, 1,3-1,4-Beta-Glucanase; 1,4-Alpha Maltotetrahydrolase; nefazodone, nelfinavir, niclosamide, nilutamide, nitaZOX 1,4-Alpha-D-Glucan Glucanohydrolase; 1,4-Beta-D-Glucan anide, nizatidine, nofetumomab, norfloxacin, octreotide, Cellobiohydrolase Cel7; 1,4-Beta-D-Glucan Cellobiohydro ofloxacin, olanzapine, omeprazole, oxacillin, oxaliplatin, lase I: 1,4-dihydropyridine Receptor on alpha1 subunit of oxazepam, oxiconazole, oxytocin, pamidronate, pantopra L-type Voltage sensitive Ca2+ channels; 10 Kda Chaperonin; Zole, paramethasone, paroxetine, pegaptainib, penicillamine, 10-Formyltetrahydrofolate Dehydrogenase; 1'-cis retinol penicilling benzathine, penicillin V, pentetate, pentosan dehydrorgenase; 12-Oxophytodienoate Reductase; 12-Oxo polysulfate, perflexane, perflubron, perfluoropolymethyliso phytodienoate Reductase 1: 12-Oxophytodienoate-10, 11 propyl ether, perflutren, pergolide, permethrin, perphenazine, Reductase: 14-3-3-Like Protein C: 15-hydroxyprostaglandin phenoxybenzamine, pimecrolimus, pimozide, pioglitaZone, dehydrogenase NAD+: 17-Beta-Hydroxysteroid Dehydro piperacetazine, piperacillin, pipobroman, piroxicam, polythi genase; 17-Beta-Hydroxysteroid Dehydrogenase 4; 17 Kd azide, porfimer, potassium salts, povidone-iodine, pramipex Fetal Brain Protein: 19-Mer Peptide Fragment OfRhodopsin: ole, pramlintide, prazepam, prednisolone, probenecid, probu 1-Aminocyclopropane-1-Carboxylate Deaminase; 1-Deoxy col, prochlorperazine, proguanil, promazine, promethazine, D-Xylulose 5-Phosphate Reductois; 1-Pyrroline-5-Carboxy propiomazine, propyliodone, propylthiouracil, late Dehydrogenase; 1 SY6:HOKT3 Heavy Chain 1; 1SY6:L pyrimethamine, pyrithione Zinc, quazepam, quetiapine, OKT3 Light Chain 1: 2,2-Dialkylglycine Decarboxylase; US 2008/0220441 A1 Sep. 11, 2008

2,3-Bisphosphoglycerate-Independent Phosphog: 2,3-Dihy Dioxygenase: 4-Hydroxythreonine-4-Phosphate Dehydro droxybenzoate-Amp Ligase: 2,3-Dihydroxybiphenyl Dioxy genase; 4M5.3 Anti-Fluorescein Single Chain Antibody; genase; 2.3-Dihydroxybiphenyl-1,2-Dioxygenase; 2,4-Di 4-Oxalocrotonate Tautomerase: 4'-Phosphopantetheinyl enoyl-Coa Reductase; 2,5-Diketo-D-Gluconic Acid Transferase Sfp: 4-trimethylaminobutyraldehyde dehydroge Reductase: 23-Kda Polypeptide Of Photosystem II Oxygen-: nase; 5,10-Methenyltetrahydrofolate Synthetase; 5,10-Meth 23S Ribosomal; 23S Ribosomal RNA; 23S rRNA of 50S ylenetetrahydrofolate Dehydrogenase; 5,10-Methylenetet ribosomal subunit; 25-hydroxyvitamin D-1 alpha hydroxy rahydrofolate Reductase: 50S Ribosomal Protein L1P, 50S lase, mitochondrial; 2'-5'-Oligoadenylate Synthetase 1; 26S subunit of the 70S ribosome of bacteria: 5-alpha reductase 1: proteasome non-ATPase regulatory subunit 1, 2-amino-3- 5-Aminolaevulinic Acid Dehydratase: 5-aminolevulinate ketobutyrate coenzyme Aligase; 2-Amino-4-Hydroxy-6-Hy synthase: 5-Aminolevulinic Acid Dehydratase; 5'-AMP-acti droxymethyldihydropte: 2-amino-4-hydroxy-6-hydroxym vated protein kinase, beta-2 subunit; 5'-AMP-activated pro ethyldihydropteridine pyrophosphokinase; tein kinase, catalytic alpha-1 chain; 5'-D: 5'-Deoxy-5'-Meth 2-Aminoethylphosphonate-Pyruvate Aminotr; 2-C-Methyl ylthioadenosine Phosphorylas; 5-Enolpyruvylshikimate-3- D-Erythritol 2.4-Cyclodiphosphate: 2-C-Methyl-D-Erythri Phosphate Synthase; 5-Epi-Aristolochene Synthase: tol 4-Phosphate Cytidyl); 2C-Methyl-D-Erythritol-2,4-Cy 5'-Fluoro-5'-Deoxyadenosine Synthase; 5-HT1A Receptor; clodiphosphate: 2-Dehydro-3-Deoxyphosphooctonate 5-HT-1B Receptor; 5-HT1D Receptor; 5-HT2A Receptor; Aldolase: 2-Enoyl-Coa Hydratase: 2-Haloacid Dehaloge 5-HT-3 Receptor; 5HT4 receptor; 5-hydroxytryptamine 1E nase: 2-Isopropylmalate Synthase: 2-Keto-3-Deoxy Glucon receptor; 5-hydroxytryptamine 1F receptor; 5-hydrox ate Aldolase; 2-Keto-3-Deoxygluconate Kinase: 2-oxoglut ytryptamine 2C receptor; 5-hydroxytryptamine 7 receptor; arate dehydrogenase E1 component, mitochondrial 5-Methyltetrahydrofolate S-Homocysteine; 5-Methyltet precursor; 2-Pyrone Synthase; 3 beta-hydroxysteroid dehy rahydrofolate S-Homocysteine Meth: 5-Methyltetrahy drogenase/delta 5-; 3.2-Trans-Enoyl-Coa Isomerase, Mito dropteroyltriglutamate-: 5-Methyltetrahydropteroyltri chondrial: 3,4-Dihydroxy-2-Butanone 4-Phosphate Syn glutamate-Homo; 5'-Methylthioadenosine Phosphorylase; thase; 3',5'-Cyclic Nucleotide Phosphodiesterase 2A; 30S 5'-Nucleotidase; 5'-R: 6,7-Dimethyl-8-Ribityllumazine Syn ribosomal protein S12:30S ribosomal protein S4; 30S Ribo thase; 6-Deoxyerythronolide B Hydroxylase; 6-Hydroxym somal Protein S6:30S ribosomal protein S9; 32.1 Kda Protein ethyl-7,8-Dihydropterin Pyrophosph; 6-Oxocamphor In Adh3-Rcal Intergenic; 33 Kda Chaperonin; 3'-5' Exonu Hydrolase; 6-Phospho-Beta-D-Galactosidase; 6-Phospho clease Eri1; 36 Kda Soluble Lytic Transglycosylase; 367Aa Beta-Glucosidase; 6-Phosphofructo-2-Kinase/Fructose-2,6- Long Hypothetical Cytochrome P450; 385Aa Long Con Bisp; 6-Phosphofructo-2-Kinase/Fructose-2,6-Bipho: served Hypothetical Protein: 3-Alpha, 20-Beta-Hydroxys 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisph; 6-Phosphof teroid Dehydrogenase; 3-Alpha-Hydroxysteroid Dehydroge ructokinase; 6-Phosphogluconate Dehydrogenase; 6-Phos nase; 3 Alpha-Hydroxysteroid Dehydrogenase Type 3: phogluconolactonase; 6-Pyruvoyl Tetrahydropterin Syn 3-Alpha-Hydroxysteroid/Dihydrodiol Dehydrogease; 3-Car thase; 7 Alpha-Hydroxysteroid Dehydrogenase; 7.8- boxy-Cis.Cis-Muconate Cycloisomerase: 3-Dehydroquinate Diamino-Pelargonic Acid Aminotransferase; 7.8-Dihydro-6- Dehydratase; 3-Dehydroquinate Dehydratase Arod; 3-Dehy Hydroxymethylpterin-Pyrophosp;70 Kilodalton Heat Shock droquinate Synthase; 3-Deoxy-D-Arabino-Heptulosonate-7- Protein: 70-Kda Soluble Lytic Transglycosylase; 7-dehydro Phosphatase; 3-Deoxy-Manno-Octulosonate Cytidylyltrans cholesterol reductase; 8-Amino-7-Oxononanoate Synthase: fer;3-Hydroxy-3-Methylglutaryl-CoaSynthase: 3-Hydroxy 8-Oxoguanine DNA Glycosylase; 92 Kda Type IV Collage 3-Methylglutaryl-Coenzyme A Reductase; 3-Hydroxyacyl nase; A chain, A/G-Specific Adenine Glycosylase; Aac; Coa Dehydrogenase; 3-Hydroxyacyl-Coa Dehydrogenase Aah2: Lch-Alpha-It: Abc Transporter, ATP Binding Protein; Type II: 3-hydroxyisobutyrate dehydrogenase, mitochondrial Acetate Kinase; Acetoacetyl-Coa Thiolase; Acetohydroxy precursor, 3-Isopropylmalate Dehydrogenase; 3-Ketoacetyl Acid Isomeroreductase; Acetohydroxy-Acid Synthase; Coa Thiolase: 3-Keto-L-Gulonate 6-Phosphate Decarboxy Acetoin Reductase; Acetolactate Synthase, Catabolic; Aceto lase; 3-keto-steroid reductase: 3-Mercaptopyruvate Sul lactate Synthase, Mitochondrial; Acetyl Group: Acetyl Trans furtransferase: 3-Methyl-2-Oxobutanoate ferase: Acetyl Xylan Esterase: Acetylcholine Binding Pro Hydroxymethyltra; 3-Methyl-2-Oxobutanoate Hydroxym tein: Acetylcholine-Binding Protein: Acetylcholinesterase: ethyltransfe: 3-Methyladenine DNA Glycosylase; 3-Methy Acetylcholinesterase: Acetylcholinesterase (AChE); Acetyl laspartate Ammonia-Lyase, 3-oxo-5-alpha-steroid 4-dehy cholinesterase precursor; Acetyl-Coa Acetyltransferase; drogenase 2: 3-Oxoacyl-, 3-Oxoacyl-Acyl-Carrier Protein Acetyl-CoA Acetyltransferase (Mitochondrial); Acetyl-Coa Reductase: 3-Oxoacyl-Acyl-Carrier Protein Synthas; Carboxylase; Acetyl-CoA carboxylase 2: Acetyl-Coa Syn 3-Oxoacyl-Acyl-Carrier-Protein Synthas; 3-oxoacyl-acyl thetase: Acetyl-Coenzyme AAcetyltransferase 2: Acetyl-Co carrier-protein synthase I: 3-oxoacyl-acyl-carrier-protein enzyme A Carboxylase; Acetyl-Coenzyme A Synthetase 1: synthase II: 3-oxoacyl-acyl-carrier-protein synthase III; Acetyl-coenzyme A synthetase 2-like, mitochondrial; 3-Phosphoglycerate Kinase; 3-Phosphoinositide Dependent Acetyl-coenzyme A synthetase, cytoplasmic; Acetyl Protein Kin; 3-Phosphoinositide Dependent Protein Kinase-; glutamate Kinase; Acidic Fibroblast Growth Factor; Acidic 3-Phosphoshikimate 1-Carboxyvinyltransferase: 3-Phytase Lectin; Acireductone Dioxygenase; Aclacinomycin Methyl A; 47 Kda Membrane Antigen: 4-Alpha-Glucanotransferase: esterase; Aclacinomycin-10-Hydroxylase; Aconitase; Aconi 4-Amino-4-Deoxychorismate Lyase: 4-Aminobutyrate Ami tate Hydratase; Aconitate Hydratase 2: Acriflavine Resis notransferase: 4-Chlorobenzoyl Coa Ligase: 4-Chloroben tance Protein B; Actagardine; Actin; Actin Alpha 1: Actin Zoyl Coenzyme A Dehalogenase, 4-Cresol Dehydrogenase Depolymerizing Factor; Actin, Alpha Skeletal Muscle; Actin Hydroxylating Flavo: 4-Diphosphocytidyl-2-C-Methyl-D- Fragmin Kinase; Activated Cdc42 Kinase 1: Activator Of Erythrit: 4-Diphosphocytidyl-2-C-Methylerythritol Synt; Activin receptor; Activin Receptor Type II: Actva-Orf6 4-Hydroxybenzoyl-Coa Thioesterase: 4-Hydroxyphe Monooxygenase; Acutohaemonlysin; Acyl Carrier Protein; nylpyruvate Dioxygenase, 4-Hydroxyphenylpyruvic Acid Acyl Carrier Protein Phosphodiesterase: Acyl Carrier Protein US 2008/0220441 A1 Sep. 11, 2008 42

Synthase; Acyl carrier protein, mitochondrial precursor, Aldehyde oxidase; Aldehyde Oxidoreductase; Aldehyde Acyl-Acyl-Carrier Protein Desaturase: Acyl-Acyl-Carrier Reductase; Aldo-Keto Reductase Family 1 Member C1; Protein-Udp-N-Acetylgl; Acylamino-Acid-Releasing Aldo-keto reductase family 1 member C2; Aldo-Keto Reduc Enzyme: Acyl-Coa Dehydrogenase; Acyl-CoA dehydroge tase Family 1 Member C3; Aldo-keto reductase family 1 nase family member 8: Acyl-Coa Dehydrogenase Family member C4; Aldolase; Aldolase Protein; Aldose 1-Epime Member 8, Mito. Acyl-Coa Dehydrogenase, Medium-Chain rase; Aldose Reductase; Alginate Lyase; Algal; Algo2; ALK Specifi, Acyl-CoA dehydrogenase, short-chain specific, tyrosine kinase receptor, Alkaline Phosphatase; Alkaline mitochondrial precursor; Acyl-Coa Hydrolase; Acyl-Coa Phosphatase: Alkyl Hydroperoxide Reductase Subunit F: Oxidase; Acyl-CoaThioesterase I: Acyl-Coa Thioesterase II; Allantoate Amidohydrolase; Allene Oxide Synthase-Lipoxy Acyl-Coenzyme A Binding Protein; acyl-coenzyme A: cho genase Protein; Alliin Lyase; Alpha Amylase; Alpha Glu lesterol acyltransferase; Acylphosphatase; Adam 33: Ada tathione S-Transferase: Alpha, Alpha-Trehalose-Phosphate malysin II: Adenine Glycosylase; Adenine Phosphoribosyl Synthase; Alpha-1 Catenin, Alpha1.2-Mannosidase; Alpha transferase; Adenine-N6-DNA-Methyltransferase Taqi; 1.2-Mannosidase; Alpha-1,3-Mannosyl-Glycoprotein Beta Adenosine 2B receptor, Adenosine A1 receptor, Adenosine 1.2-N-; Alpha-1,4-Galactosyl Transferase: Alpha-1,4-Glu A3 receptor; Adenosine Deaminase; Adenosine Kinase; can-4-Glucanohydrolase; Alpha-1,4-N- Adenosylcobinamide Kinase; Adenosylhomocysteinase; Acetylhexosaminyltransferase Ext; Alpha-1A Adrenergic Adenosylmethionine-8-Amino-7-Oxononanoat, Adenosyl Receptor; Alpha1-Antitrypsin; Alpha-1-Antitrypsin, Alpha methionine-8-Amino-7-Oxononanoate Am; Adenylate 1B adrenergic receptor, Alpha-1D adrenergic receptor; Cyclase; Adenylate cyclase (cAMP); Adenylate Kinase; Ade Alpha-1-Purothionin; Alpha-2.3/8-Sialyltransferase: Alpha nylate Kinase 1: Adenylate Kinase Isoenzyme-3; Adenylo 2A Adrenergic Receptor; Alpha-2B adrenergic receptor; Succinate Synthetase; AdenyloSuccinate synthetase isozyme Alpha-2C adrenergic receptor; Alpha-2-Macroglobulin; 1: Adenylyl Cyclase; Adenylylsulfate Kinase; Adipocyte Alpha-2U-Globulin; Alpha-aminoadipic semialdehyde syn Lipid Binding Protein: Adipocyte Lipid-Binding Protein; thase, mitochondrial precursor, Alpha-Amylase; Alpha ADP Compounds Hydrolase Nude; ADP, ATP Carrier Protein Amylase I: Alpha-Amylase II; Alpha-Amylase Isozyme 1: Heart Isoform T1: ADPATP carrier protein, fibroblast iso Alpha-Amylase, Pancreatic; Alpha-Amylase, Salivary; form; ADPATP carrier protein, heart/skeletal muscle isoform AlphaChain (LH); Alpha-Conotoxin Gid: Alpha-D-Glucose T1:ADPATP carrier protein, liver isoform T2: ADP-Depen 1,6-Bisphosphate Phosphotran; Alpha-D-Glucuronidase; dent Glucokinase; ADP-L-Glycero-D-Mannoheptose 6-Epi Alpha-Galactosidase; Alpha-Galactosidase A.; Alpha-Glu merase: Adpr Pyrophosphatase; ADP-Ribose Pyrophos cosidase; Alpha-Glucosidase; Alpha-Glucuronidase; Alpha phatase; ADP-Ribosyl Cyclase; ADP-Ribosylation Factor 1: Ketoglutarate-Dependent Taurine Dioxyg: Alpha-L-Ara ADP-Ribosylation Factor 2; ADP-Ribosylation Factor 4: binofuranosidase; Alpha-L-Arabinofuranosidase B: Alpha ADP-Ribosylation Factor 6; ADP-Ribosylation Factor-Like Lytic Protease; Alpha-Mannosidase II; Alpha-Momorcharin; 8; ADP-Ribosylation Factor-Like Protein 1; ADP-Ribosyla Alpha-Momorcharin Complexed With Adenine: Alpha-Mo tion Factor-Like Protein 3; ADP-Ribosylation Factor-Like morcharin Complexed With Formycin; Alpha-N-Acetylga Protein 5; ADP-Ribosyltransferase; Adrenodoxin; Adreno lactosaminidase; Alpha-N-acetylgalactosaminidase precur doxin Reductase; Adsorption Protein P2: Aequorin; Aequorin sor; Alpha-N-acetylglucosaminidase precursor; Alpha 2: Aeromonas caviae: AFG3-like protein 1: AFG3-like pro Neurotoxin Tx12: Alpha-Tocopherol Transfer Protein; tein 2: Agglutinin; Agglutinin; Agglutinin Isolectin 3; Agglu Alpha-Trehalose-Phosphate Synthase; Alpha-Trichosanthin tinin Isolectin I/Agglutinin Isolect; Agglutinin Isolectin Vi; Complexed With Adenine; Amic; Amicyanin; Amidase Agglutinin Isolectin Vi/Agglutinin Isolec; Agmatinase; Operon; Amidophosphoribosyltransferase; Amidophospho Agmatine Iminohydrolase; Agrobacterium Timefaciens Dps; ribosyltransferase precursor; Amidophosphoribosyltrans Ahplaao; Aicar Transformylase-Imp Cyclohydrolase; ferase precursor; Amidotransferase Hish; Amiloride-sensi Alamethicin; Alanine aminotransferase; Alanine Dehydroge tive amine oxidase copper-containing precursor; nase; Alanine Racemase; Alanine racemase, biosynthetic; Amiloride-sensitive cation channel 1, neuronal; Amiloride Alanine-Glyoxylate Aminotransferase; Alanine-glyoxylate sensitive cation channel 2, neuronal; Amiloride-sensitive aminotransferase 2: Alanyl-tRNA synthetase; Alcohol Dehy Sodium channel alpha-Subunit; Amiloride-sensitive sodium drogenase; Alcohol Dehydrogenase; Alcohol dehydrogenase channel beta-Subunit; Amiloride-sensitive Sodium channel NADP+: Alcohol dehydrogenase 6: Alcohol Dehydroge delta-Subunit; Amiloride-sensitive sodium channel gamma nase Alpha Chain; Alcohol Dehydrogenase Beta Chain; Alco subunit; Amine Oxidase; Amine Oxidase Flavin-Contain holdehydrogenase class II pichain precursor, Alcohol Dehy ing A; Amine Oxidase Flavin-Containing. B; Amine Oxi drogenase Class III Chi Chain; Alcohol dehydrogenase class dase, Copper Containing; Amine Oxidase, Flavin IV mu?sigma chain; Alcohol Dehydrogenase Class IV Sigma Containing; Aminoacylase-1; Aminoglycoside 2'-N- Chain; Alcohol Dehydrogenase E Chain; Alcohol Dehydro acetyltransferase; Aminoglycoside 3'-Phosphotransferase; genase Gamma Chain; Alcohol Dehydrogenase, Class II; Aminoglycoside 6'-N-Acetyltransferase; Aminomethyl Alcohol Dehydrogenase, Class II; Alcohol Dehydrogenase, transferase; Aminopeptidase; Aminopeptidase P, Ami Iron-Containing; Alcohol Sulfotransferase; Aldehyde Dehy notransferase; Aminotransferase, Putative; Amnionless pro drogenase; Aldehyde Dehydrogenase; Aldehyde dehydroge tein; AMP deaminase 1: Amp Nucleosidase; AMP-activated nase 1A3; Aldehyde dehydrogenase 3B1; Aldehyde dehydro protein kinase (AMPK); AMT protein; Amyloid Beta-Pep genase 3B2; Aldehyde dehydrogenase family 7 member Al; tide; Amyloid protein-binding protein 1; Amylomaltase; Aldehyde dehydrogenase X, mitochondrial precursor; Alde Amylosucrase; Anabaena Sensory Rhodopsin; Anaerobic hyde Dehydrogenase, Cytosolic 1: Aldehyde dehydrogenase, Ribonucleotide-Triphosphate Reduct; Androgen Receptor; dimeric NADP-preferring; Aldehyde Dehydrogenase, Mito Angiogenin; Angiostatin; Angiotensin Converting Enzyme; chondrial Precur; Aldehyde dehydrogenase, mitochondrial Angiotensin-converting enzyme (ACE); Annexin A1, precursor; Aldehyde Ferredoxin Oxidoreductase Protein C: Annexin III; Annexin V: Anthocyanidin Synthase; Anthra US 2008/0220441 A1 Sep. 11, 2008 nilate Phosphoribosyltransferase: Anthranilate Phosphoribo Bacteriophage Lambda Lysozyme; Bacteriophage T4 Short syltransferase 2: Anthrax Toxin Receptor 2: Anti IgE anti Tail Fibre; Bacteriorhodopsin; Baculoviral lap Repeat-Con bodyVH domain chain 1: Anti IgE antibodyVL domain chain taining Protein 4; Bap1; Basement Membrane Protein 1; Antibody Vhh Lama Domain; Antifungal Protein 1: Anti Bm-40; Basic Fibroblast Growth Factor; Basic Phospholi gen 85B; Antigen 85-C; Anti-H; Anti-Muellerian hormone pase A2: Bba1; Bba5: B-cell receptor; Benzoate 1,2-Dioxy type II receptor; Anti-Platelet Protein; Anti-Sigma F Factor genase Reductase; BenZodiazepine Receptor, Benzoylfor Antagonist; Antithrombin III (ATIII); Antithrombin-III: mate Decarboxylase; Benzyl Alcohol Dehydrogenase; Beta 1 Antiviral Protein 3: Antiviral Protein S; Apag Protein; adrenergic receptor, Beta 1.4 Galactosyltransferase; Beta 2 Apc35852; Apc35880; Apical Membrane Antigen 1: Apoc adrenergic receptor; beta chain (FSH); Beta Crystallin B1; arotenoid-Cleaving Oxygenase; Apoferritin Co-Crystallized Beta Lactamase; Beta platelet-derived growth factor receptor With Sn-Protopor; Apolipoprotein; Apollipoprotein A-II; precursor, Beta Trypsin; Beta-(1,3)-glucan synthase Frag Apoptosis regulator Bcl-2; Apoptotic Protease Activating ment: Beta-1,4-D-Glycanase Cex-Cd; Beta-1,4-Galacta Factor 1; Apyrase; Aquaporin 1: Aquaporin Z; Arabinan nase; Beta-1,4-Galactosyltransferase, Beta-1,4-Galactosyl Endo-1,5-Alpha-L-Arabinosidase A: Arabinan-Endo 1.5-Al transferase 1: Beta-1,4-Mannanase; Beta2-Glycoprotein-1; pha-L-Arabinase; Arabinose Operon Regulatory Protein; Beta3 Alcohol Dehydrogenase; Beta-adrenergic receptor Arac, Arachidonate 15-lipoxygenase; Arachidonate 5-li kinase 1: Beta-adrenergic receptor kinase 2: Beta-Agarase A: poxygenase; A-Rafproto-oncogene serine/threonine-protein Beta-Alanine Synthase: Beta-Amylase; Beta-B2-Crystallin; kinase; Arcelin-1-Arcelin-5A; Archaeal Sm-Like Protein Af. Beta-Carbonic Anhydrase: Beta-Catenin; BetaChain; Sm2; Archaeosine tRNA-Guanine Transglycosylase; Argin BetaChain (LH); Beta-Conglycinin, Beta Chain; Beta-Cryp ase; Arginase 1: Arginase I; Arginase II; Arginase II, Mito togein; Beta-D-Glucan Exohydrolase Isoenzyme Exo 1: chondrial Precursor, arginine decarboxylase; Arginine Beta-D-Glucan Glucohydrolase Isoenzyme Exo1; Beta-Elic Kinase; Arginine N-Succinyltransferase, Alpha Ch; Argini itin Cryptogein; Beta-Fructosidase; Beta-Galactosidase; noSuccinate Synthase; Argininosuccinate synthase Frag Beta-Galactoside-Binding Lectin; Beta-Glucosidase; Beta ment; Argininosuccinate Synthetase; Arginosuccinate lyase; Glucosidase A. Beta-Glucosyltransferase: Beta-Glucu Arginosuccinate synthase; Aristolochene Synthase; Arnb ronidase; Beta-Hexosaminidase; Beta-Hexosaminidase Beta Aminotransferase; Arno; Aromatase; Aromatic Amino Acid Chain; Beta-Hordothionin; Beta-Hydroxydecanoyl Thiol Aminotransferase; Arpg836; Arsenate Reductase; Arsenical Ester Dehydrase; Betaine-Homocysteine Methyltransferase: pump-driving ATPase; Arsenical Resistance Operon Repres Betaine-Homocysteine S-Methyltransferase: Beta-Keto Acyl sor, Pu; Arsenite-Translocating Atpase; Arthropodan Carrier Protein Reductase: Beta-Ketoacyl Acyl Carrier Pro Hemocyanin; Artificial Nucleotide Binding Protein; Arto tein Synthas; Beta-Ketoacyl-Acyl-Carrier-Protein Syn carpin; Aryl Sulfotransferase: Arylamine N-Acetyltrans thas; Beta-Ketoacyl-Acp Synthase III: Beta-Ketoacyl-Acyl ferase; Arylsulfatase; Arylsulfatase A: Arylsulfatase A: Carrier Protein Synth; Beta-Ketoacyl-Acyl Carrier Protein Ascorbate Oxidase; Ascorbate Peroxidase; Asparagine Syn Synthase: Beta-Ketoacylsynthase III: Beta-Lactam Syn thetase; Asparagine Synthetase B; Asparaginyl-tRNA syn thetase; Beta-Lactamase; Beta-Lactamase CtX-M-14; Beta thetase; Aspartate 1-Decarboxylase; Aspartate 1-Decarboxy Lactamase CtX-M-27; Beta-Lactamase CtX-M-9; Beta-Lac lase Precursor, Aspartate Aminotransferase; Aspartate tamase II: Beta-Lactamase Imp-1: Beta-Lactamase Oxa-1: Aminotransferase; Aspartate aminotransferase, cytoplasmic; Beta-Lactamase Oxa-10; Beta-Lactamase Oxa-2: Beta-Lac Aspartate aminotransferase, mitochondrial; Aspartate Dehy tamase Pse-2, Beta-Lactamase ShV-1; Beta-Lactamase Shv drogenase; Aspartate Receptor, Aspartate Transcarbamoy 2. Beta-Lactamase Tem; Beta-Lactamase. Type II: Beta-Lac lase; Aspartate-Semialdehyde Dehydrogenase; Aspartic Pro toglobulin; Beta-Mannanase; Beta-Mannosidase; Beta tease Bla G. 2; Aspartic Proteinase; Aspartoacylase; Asparty1 Methylaspartase: Beta-Momorcharin; Beta-N- aminopeptidase; Asparty1/asparaginyl beta-hydroxylase; Acetylhexosaminidase; Beta-N-Acetylhexosaminidase; Aspartyl-tRNA Synthetase: Aspergillopepsin; Assemblin; Beta-Phosphoglucomutase; Beta-Purothionin; Beta-Secre Astacin: At5G 11950; ATP Phosphoribosyltransferase: ATP tase 1: Beta-Spectrin; Beta-Trypsin; Beta-Tryptase: Bh()236 Sulfurylase: ATP Synthase; ATP synthase delta chain, mito Protein; Bifunctional 3'-Phosphoadenosine 5'-Phospho: chondrial Precursor; ATP-binding cassette: ATP-Depen Bifunctional adenosylcobalamin biosynthesis protein cobU: dent Clp Protease ATP-Binding Subun; ATP-Dependent Bifunctional aminoacyl-tRNA synthetase: Bifunctional DNA Helicase: ATP-Dependent Hsl Protease ATP-Binding Deaminase/Diphosphatase: Bifunctional Dihydrofolate S; ATP-Dependent Metalloprotease Ftsh; ATP-Dependent Reductase-Thymidy; Bifunctional dihydrofolate reductase RNA Helicase P54: ATP-Phosphoribosyltransferase: ATP thymidylate synthase: Bifunctional Histidine Biosynthesis sensitive inward rectifier potassium channel 1: ATP-sensitive Prot; Bifunctional methylenetetrahydrofolate dehydroge inward rectifier potassium channel 11; Atrial Natriuretic Pep nase/cyclohydrolase; Bifunctional P-450: Nadph-P450 tide Clearance Recepto; Atrial natriuretic peptide receptor A: Reductase: Bifunctional PGK/TIM Includes: Phosphoglyc Atrial Natriuretic Peptide Receptor A; Atrolysin C; Aug erate kinase, EC 2.7.2.3, Triosephosphate isomerase, EC5.3. menter Of Liver Regeneration: Aurora-Related Kinase 1: 1.1, TIM, Triose-phosphate isomerase: Bifunctional Purine Autocrine Motility Factor; Autoinducer-2 Production Protein Biosynthesis Protein Pur: Bifunctional purine biosynthesis Luxs; Autolysin; Auxin Binding Protein 1: Avermectin-Sen protein PURH Includes: Phosphoribosylaminoimidazole sitive Chloride Channel GI; Avian Sarcoma Virus Integrase: carboxamide formyltransferase, EC 2.1.2.3, AICAR trans Avidin; Axin; AZurin; B chain; B Lymphocyte Stimulator; formylase, IMP cyclohydrolase, EC 3.5.4.10, Inosinicase, B4Dimer; B9340; Bacterial azoreductase (Bacillus sp); Bac IMP synthetase, ATIC: Bifunctional Puta Protein: Bifunc terial isoleucyl-tRNA synthetase; Bacterial Leucyl Ami tional Rela/Spot; Bikunin; Bile Acid Receptor; Bile salt nopeptidase; Bacterial membranes; Bacterial Sialidase; Bac export pump; Bile-Salt Activated Lipase; Biliary Glycopro terial Sulfite Oxidase; Bactericidal/Permeability-Increasing tein C: Bilin Binding Protein; Bilin-Binding Protein; Biliver Protein; Bacteriochlorophyll A Protein; Bacterioferritin: din IX Beta Reductase; Biliverdin Reductase A; Biliverdin US 2008/0220441 A1 Sep. 11, 2008 44 reductase A precursor: Bioh Protein; Biosynthetic Thiolase; echol Oxidase; Catechol-O-Methyltransferase: Catechol-O- Biotin Synthase; biotinidase; biotin-protein ligase; Biphenyl methyltransferase (COMT): Cathepsin B: Cathepsin F; 2,3-Diol 1,2-Dioxygenase; Bleomycin Resistance Determi Cathepsin G: Cathepsin K; Cathepsin S: Cathepsin V: Cation nant; Bleomycin Resistance Protein; Bleomycin-Binding Dependent Mannose-6-Phosphate Recepto: Cation-Depen Protein; Blood Coagulation Factor Vii; Blue Fluorescent Pro dent Mannose-6-Phosphate Recepto: Cationic amino acid tein; B-Luffin; Bm-40; Bone Marrow Stromal Cell Antigen 1: transporter-3; Cationic amino acid transporter-4; Cation-In Bone Morphogenetic Protein 2: Bone Morphogenetic Protein dependent Mannose 6-Phosphate Recep: Cbp21; Cd2; CD2 7; Botulinum Neurotoxin Type B; Bovine Beta-Lactoglobu lymphocyte antigen; CD20 B-lymphocyte antigen; CD33 lin A; Bowman-Birk Inhibitor Derived Peptide; Bp40; Brady antigen; Cd46; CD52 Antigen; Cd58; Cd59 Complexed With kinin; B-Raf proto-oncogene serine/threonine-protein Glcnac-Beta-1,4-Glcnac-Be; Cdc25 B-Type Tyrosine Phos kinase; Branched-chain alpha-ketoacid dehydrogenase phatase; Cdc42Hs-GDP; Cdp-Glucose 4,6-Dehydratase: kinase; Branched-Chain Amino Acid Aminotransferase; Cdp-Glucose-4,6-Dehydratase; Cdp-Tyvelose-2-Epimerase: Branched-Chain Amino Acid Aminotransferase, Branched CEA or carcinoembryonic antigen-multiple sequences; Cell chain-amino-acid aminotransferase, cytosolic; Branched Cycle Arrest Protein Bub3; Cell Division Control Protein 2 chain-amino-acid aminotransferase, mitochondrial; Homolog: Cell Division Control Protein 6: Cell Division Brazzein; Bruton S Tyrosine Kinase; BseG341 Restriction Inhibitor; Cell Division Protein Ftsy: Cell division protein Endonuclease; Butyryl-Coa Dehydrogenase; C Protein ftsZ: Cell Division Protein FtsZ. Homolog 1: Cell Division Alpha-Antigen; C. pasteurianum Hydrogenase I: C-1027 Protein Kinase 2: Cell Division Protein Kinase 7: Cell Divi Apoprotein; C1R Complement Serine Protease: C-1-tetrahy sion Protein Zipa: Cell Wall Pentapeptide Ala-: Cell Wall drofolate synthase: C-4 methylsterol oxidase; C4-Dicarboxy Peptide In Complex With Deglucobalhi: Cellobiohydrolase; late Transport Transcriptional R; Caffeic Acid 3-O-Methyl Cellobiohydrolase CeléA; Cellobiohydrolase I: Cellobiohy transferase; Caffeoyl-Coa O-Methyltransferase: Cag-Z: drolase I Catalytic Domain: Cellobiohydrolase II: Cellobiose Calcineurin B subunit isoform 1: Calcineurin B-Like Protein Dehydrogenase; Cellular retinaldehyde-binding protein: Cel 4, Calcitonin, Calcitonin Analogue; Calcitonin receptor, Cal lular retinoic acid binding protein 1: Cellular retinoic acid cium/Calmodulin-Dependent 3',5'-Cycli; Calcium/Calm binding protein 2: Cellulase; Cellulase B: Cellulase Cel48F: odulin-Dependent Protein Kinase; calcium-activated potas Cellulase Cel9M; Cellulase Celc: Cellulomonas Fimi Family sium channel; Calcium-binding mitochondrial carrier protein 10 Beta-1,4-Glycana; Cellulosomal Scaffoldin; Cephaibol B; Aralarl; Calcium-binding mitochondrial carrier protein Cephalosporin C Deacetylase; Cephalosporinase; Ceramide Aralar2: Calcium-Dependent Protease, Small Subunit; Cal glucosyltransferase: Ceruloplasmin Cg 14704 Protein:cCMP cium-transporting ATPase type 2C member 1, CalgizZarin; Phosphodiesterase; Cgmp Phosphodiesterase A2; Cgmp-In Calmodulin, Calpain 1, Large Catalytic Subunit; Camp hibited 3',5'-Cyclic Phosphodiesteras; Cgmp-Specific 3',5'- Dependent Protein Kinase; cAMP Phosphodiesterase: Cyclic Phosphodiesterase; Chalcone Synthase; Chalcone Camp-Dependent Protein Kinase; Camp-Dependent Protein Synthase 2: Chalcone-Flavonone Isomerase 1: Chalcone-Fla Kinase Regulatory Sub: Camp-Dependent Protein Kinase Vonone Isomerase 1: Chaperone Protein Htpg: C-Ha-Ras: Type 1; Camp-Dependent Protein Kinase Type I-Alpha R: Charybdotoxin: Chemosensory Protein A6; Chemotactic Camp-Dependent Protein Kinase, Alpha-Cat; Camp-Specific Peptide; Chemotaxis Protein Chea; Chemotaxis Protein 3',5'-Cyclic Phosphodieste; Camp-Specific 3',5'-Cyclic Phos Chey; Chemotaxis Receptor Methyltransferase Chem.; Chi phodiesterase; cAMP-specific 3',5'-cyclic phosphodiesterase mera Of Glutathione S-Transferase-Synthet; Chimera Of 7B; Camp-Specific Phosphodiesterase Pde4D2: Cannabinoid Maltose-Binding Periplasmic Prote: Chitinase; Chitinase; receptor 2; Cannabinoid Receptors; Capsid Protein C; Capsid Chitinase 1: Chitinase A; Chitinase A; Chitinase B: Chitinase Protein P40; Capsid Protein P40: Assemblin Protease; Cara: B: Chitinase-3 Like Protein 1 Chitobiase; Chitobiose Phos Carbapenem Synthase; Carbohydrate-Phosphate Isomerase: phorylase; Chitosanase; Chitotriosidase; Chitotriosidase 1: Carbon Monoxide Oxidation System Transcripti; Carbonic Chitotriosidase Synonym: Chitinase; Chloramphenicol Anhydrase; Carbonic Anhydrase I; Carbonic Anhydrase II; Acetyltransferase; Chloramphenicol Phosphotransferase: Carbonic Anhydrase III; Carbonic Anhydrase IV: Carbonic Chlorella Virus DNA Ligase-Adenylate; Chloride channel Anhydrase Xii; Carbonic Anhydrase Xiv; Carbonyl Reduc protein 2: Chloride Intracellular Channel Protein 1: Chloro tase; Carbonyl Reductase Nadph 1; Carboxy Methyl Trans catechol 1,2-Dioxygenase; Chloroperoxidase; Chloroperoxi ferase For Protein Phosp; Carboxy-Cis.Cis-Muconate dase F. Chlorophyll A-B Binding Protein Ab80; Chlorophyll Cyclase; Carboxyethylarginine Synthase; Carboxylesterase: A-B Binding Protein, Chloroplast; Chloroplast Ferredoxin Carboxylesterase Est2: Carboxylesterase Precursor; Car Nadp+ Oxidoreductase; Chloroplast Outer Envelope Protein boxymethylated Rhodanese: Carboxymuconolactone Decar Oep34; Chloroplastic Ascorbate Peroxidase; Cho Reductase: boxylase Family Pr; Carboxypeptidase A; Carboxypeptidase Cholecystokinin type A receptor; Cholera Toxin: Cholera Gp180 Residues 503-882: Carboxypeptidase M: Carboxy Toxin B Subunit; Cholesterol Esterase; Cholesterol Oxidase; Terminal Domain RNA Polymerase I; Caminomycin 4-O- Choline dehydrogenase; Choline kinase alpha; Choline Methyltransferase; Carnitine Acetyltransferase; Carnitine O-acetyltransferase: Choline/ethanolamine kinase; Choline Acetyltransferase Isoform 2; Carnitine O-acetyltransferase: phosphate cytidylyltransferase A. Choline-phosphate cytidy Carnitine O-palmitoyltransferase I, mitochondrial liver iso lyltransferase B: Cholinesterase; Choloylglycine Hydrolase; form (CPT-1); Carnitine O-palmitoyltransferase II, mito Chondroitin Ac Lyase; Chondroitinase Ac; Chondroitinase chondrial (CPT-2); Casein Kinase II, Alpha Chain; Casein B: Chorionic Gonadotropin: Chorismate Lyase; Chorismate Kinase-1, Caspase-1 precursor; Caspase-3; Caspase-7: Cata Mutase; Chorismate Synthase; Chromosomal Replication bolic Alanine Racemase Dadx; Catabolite Gene Activator; Initiator Protei: Chymase; Chymase; Chymotrypsin; chymot Catabolite Gene Activator Protein; Catalase; Catalase 1: rypsin B: Chymotrypsinogen A; Circadian Clock Protein Catalase A: Catalase Hpii; Catalase-Peroxidase; Catalase Kaib; Cis-Biphenyl-2,3-Dihydrodiol-2,3-Dehydrogena; Peroxidase Protein Katg; Catechol 1,2-Dioxygenase; Cat Cite: Citrate Lyase, Beta Subunit; Citrate Synthase: Citrate US 2008/0220441 A1 Sep. 11, 2008

Synthase; C-Kit Protein; Claret Segregational Protein; Class Gamma-Synthase; Cysteine desulfurase: Cysteine dioxyge BAcid Phosphatase; Class B Carbapenemase Blab-1; Class C nase fragment: Cysteine dioxygenase type I: Cysteine Beta-Lactamase; Class I Alpha-1,2-Mannosidase; Class-Mu sulfinic acid decarboxylase; Cysteine-Rich Domain Of Man Glutathione S-Transferase; Clavaminate Synthase 1: Clpb nose Receptor; Cysteinyl leukotriene Receptor 1: Cysteinyl Protein; Cmp-N-Acetylneuraminic Acid Synthetase; Coagul leukotriene receptor 2: Cysteinyl-tRNA Synthetase: Cystic lation Factor Ix; Coagulation Factor V: Coagulation factor Fibrosis Transmembrane Conductanc: Cystic Fibrosis Trans VII: Coagulation Factor VIII; Coagulation Factor Viii Precur membrane Conductance Re: Cystine/glutamate transporter; sor; Coagulation Factor X: Coagulation Factor Xiii; Coagul Cystinosin; Cytidine Deaminase; Cytidine Monophospho-N- lation Factor XiiiA Chain; Coagulation factor XIII A chain Acetylneuraminic Acid; Cytidylate Kinase; Cytochrome precursor; Coat Protein; Coatomer Gamma Subunit; Cob: B=5=Reductase; Cytochrome B2; Cytochrome B2, Mito Cob(I)yrinic acid a,c-diamide adenosyltransferase; Cobal chondrial; Cytochrome B5; Cytochrome B5 Outer Mitochon amin-Dependent Methionine Synthase; Cobalt-Precorrin-4 drial Membrane Is; Cytochrome B562; Cytochrome C: Cyto Transmethylase; Cocaine Esterase: Coenzyme A Biosynthe chrome C". Cytochrome C"; Cytochrome C Family Protein; sis Bifunctional Protein: Coenzyme F420-Dependent Cytochrome C Nitrite Reductase; Cytochrome c oxidase sub N5.N10-Methylenete: Coenzyme F420H2: Nadp+ Oxi unit 1; Cytochrome CPeroxidase; Cytochrome CPeroxidase, doreductase: Coenzyme Paq Synthesis Protein C: Cog4826: Mitochondrial; Cytochrome C, Iso-1; Cytochrome C. Puta Serine Protease Inhibitor; Collagen; Collagenase 3: Collage tive: Cytochrome C2; Cytochrome C2, Iso-2; Cytochrome nase-3; Collagen-Like Peptide; Complement C1R Compo C3: Cytochrome C3, A Dimeric Class III C-Type Cy; Cyto nent; Complement C1S Component; Complement C3Dg: chrome C4; Cytochrome C549; Cytochrome C550; Cyto Complement Control Protein; Complement Decay-Acceler chrome C551; Cytochrome C-551; Cytochrome C551 Per ating Factor; Complement Factor B: Complement Protein oxidase; Cytochrome C552; Cytochrome C-552; C8Gamma; Complement Receptor Type 2: COMT (catecol Cytochrome C-553; Cytochrome C-554; Cytochrome C-556; O-methyl-transferase); Conantokin-T: Conantoxin G. Con Cytochrome C6: Cytochrome C7: Cytochrome Cd1 Nitrite gerin I; Congerin II: Conjugal Transfer Protein Trwb: Con Reductase; Cytochrome CI; Cytochrome F: Cytochrome nective Tissue Activating Peptide-III: Conotoxin Gs: Oxidase Subunit II: Cytochrome P450; Cytochrome P450 Conserved Hypothetical Protein; Conserved Hypothetical 107A1; Cytochrome P450 1 19; Cytochrome P450 121; Cyto Protein Af2008: Conserved Hypothetical Protein Mth1747; chrome P450 152A1; Cytochrome P450 154C1; Cytochrome Conserved Hypothetical Protein Tm 1158: Conserved Hypo P450 17A1; Cytochrome P450 19 (Aromatase); Cytochrome thetical Protein Tm 1464; Conserved Hypothetical Protein P450 27: Cytochrome P450 2B4; Cytochrome P450 2C5; Ydce: Conserved Hypothetical Protein Yffb; Conserved Cytochrome P4502C8: Cytochrome P450 2C9; Cytochrome Hypothetical Protein Yuaa; Conserved Protein Mth1675: P450 2R1; Cytochrome P450 3A4; Cytochrome P450 4A11 Constitutive Androstane Receptor; Contryphan-R: Contry precursor; Cytochrome P450 51; Cytochrome P450 51 phan-Sm; Contryphan-Vn, Major Form; Copper Amine Oxi (Yeast); Cytochrome P450 55A1; Cytochrome P450 Bm-3: dase; Copper Amine Oxidase; Copper Amine Oxidase, Liver Cytochrome P450 Cyp119; Cytochrome P450 CYP11B1 Isozyme: Copper Transport Protein Atox1; Copper-Contain (steroid hydroxylase); Cytochrome P450Cam; Cytochrome ing Nitrite Reductase; Core Protein; Corticosteroid 11-Beta P450-Cam; Cytochrome P450Epok; Cytochrome P450Eryf: Dehydrogenase Isozyme: Corticosteroid 11-Beta-Dehydro Cytochrome P450Nor; Cytochrome Rc557: Cytoglobin: genase, Isozym; Corticosteroid 11-beta-dehydrogenase, Cytohesin 2: Cytokine Receptor Common Beta Chain; Cyto isozyme 1: Corticosteroid 11-beta-dehydrogenase, isozyme kinin Dehydrogenase 1: Cytosine Deaminase; cytosolic 2: Corticosteroid Receptor; Corticotropin Releasing Hor 5-nucleotidase II; Cytosolic phospholipase A2; Cytotoxic T mone: COX-1: COX-2; Crabp-I: Crca Protein; C-Reactive Lymphocyte Associated Antigen 4; Cytotoxic Tcell Valpha Protein; Creatine kinase B-type; Creatine kinase M-type: Domain; Cytotoxin 3: D(1B) dopamine receptor; D(2) Creatine Kinase, B Chain; Creatine kinase, sarcomeric: Cre Dopamine Receptor; D(3) Dopamine Receptor; D(4) dopam atine kinase, ubiquitous; Crk-Associated Substrate; Crotono ine receptor, D1 dopamine receptor-interacting protein cal betainyl-Coa: Carnitine Coa-Trans; Crotonobetainyl-Coa: cyon; D199S Mutant Of Bovine 70 Kilodalton Heat Sh; Carnitine Coa-Transfera; Crustacyanin; Crustacyanin A1 D206S Mutant Of Bovine 70 Kilodalton Heat Sh; D-2-Hy Subunit; Crustacyanin C2 Subunit; Cruzipain; Cryptochrome droxyisocaproate Dehydrogenase; D3, D2-Enoyl Coa 1 Apoprotein: Csdb: Csdb Protein; C-Terminal Analogue Of Isomerase Ecil; D-3-Phosphoglycerate Dehydrogenase; Neuropeptide Y. A; C-Terminal Binding Protein 1: C-Termi D-3-Phosphoglycerate Dehydrogenase; Dabd; Dahp Syn nal Binding Protein 3; C-Terminal Src Kinase; Ctla-4: Ctp thetase: D-Ala: D-Ala Ligase: D-Alanine Aminotransferase; Synthase; Ctp: Phosphocholine Cytidylyltransferase: C-Type D-Alanine: D-Lactate Ligase: D-alanine-D-alanine ligase A: Lectin Dc-Signr, Cutinase; Cyan Fluorescent Protein Cfp: D-Alanyl-D-Alanine Carboxypeptidase; D-Amino Acid Cyanate Lyase; Cyanoglobin; Cyanovirin-N; Cyclic Alpha Aminotransferase: D-Amino Acid Oxidase, D-amino-acid Melanocyte Stimulating Hormo: Cyclic Hexapeptide Rr; oxidase; D-Aminoacylase; Dape:; Daptomycin; D-beta-hy Cyclic Parathyroid Hormone; Cyclic Phosphodiesterase: droxybutyrate dehydrogenase, mitochondrial precursor; Cyclin Dependent Kinase Subunit, Type 1: Cyclin-Depen Dcoh: Ddab: De Novo Designed 21 Residue Peptide; De dent Protein Kinase 2: Cyclo: Cyclodextrin Glycosyltrans Novo Designed Cyclic Peptide; Deacetoxycephalosporin C ferase: Cyclodextrin-Glycosyltransferase: Cyclomaltodex Synthase: Death-Associated Protein Kinase; Death-Associ trin Glucanotransferase: Cyclooxygenase-2; Cyclophilin; ated Protein Kinase 1: Decorin: Dehaloperoxidase; Dehydro Cyclopropane-Fatty-Acyl-Phospholipid Syn: Cyclopropane genase/reductase SDR family member 4: Delta 2 Crystallin; Fatty-Acyl-Phospholipid Synthas; Cyclopropane-fatty-acyl Delta Crystallin I; Delta Crystallin II; Delta-1-pyrroline-5- phospholipid synthase 1: Cyclosporin A As Bound To Cyclo carboxylate dehydrogenase, mitochondrial precursor, Delta philin: Cyp175A1: CYP1A2: Cystalysin; Cystathionine Aminolevulinic Acid Dehydratase; Delta-Conotoxin Evia; Beta-Synthase. CyStathionine gamma-lyase. CyStathionine Deoxycytidine Kinase; Deoxycytidine Triphosphate Deami US 2008/0220441 A1 Sep. 11, 2008 46 nase; Deoxycytidylate Deaminase; Deoxycytidylate and Recombination Protein Rad; DNA Repair and Recombi Hydroxymethylase; Deoxy-D-Mannose-Octulosonate nation Protein Rada; DNA Repair Protein Xrcc4; DNA Rep 8-Phosphate Pho; Deoxyhypusine Synthase; Deoxyhypusine lication Protein; DNA Topoisomerase I: DNA Topoisomerase Synthase: Deoxynucleoside Monophosphate Kinase; Deox II; DNA Topoisomerase II (bacterial); DNA-3-Methylad yribodipyrimidine Photolyase; Deoxyribonuclease I: Deox enine Glycosylase I: DNA-3-Methyladenine Glycosylase II; yribonucleoside Kinase; Deoxyribose-Phosphate Aldolase; DNA-Binding Response Regulator; DNA-directed RNA Deoxyuridine 5'-Triphosphate Nucleoditohydro: Deoxyuri polymerase (E. coli); DNA-directed RNA polymerase beta dine 5'-Triphosphate Nucleotide Hydr; Deoxyuridine chain; DNA-directed RNA polymerase beta' chain; DNA 5'-Triphosphate Nucleotidohydro: Deoxyuridine Triphos Directed RNA Polymerase Subunit L: Dodecin. DOPA phatase; Dephospho-Coa Kinase; Der F II: DesGly1 Decarboxylase; Dopamine beta hydroxylase; Dopamine D1 Contryphan-R: Designed Protein Ctpr2: Designed Protein Receptor, Dopamine reuptake pump; Dp-Tt2; Dr Hemagglu Ctpr3: Dethiobiotin Synthetase; Devb Protein: Dextranase; tinin Structural Subunit; D-Ribose-5-Phosphate Isomerase: D-Galactose)-GLUCOSE BINDING PROTEIN; D-Glu D-Ribose-Binding Protein Complexed With Beta; D-Ribose cose 6-Phosphotransferase: D-Glyceraldehyde-3-Phosphate Binding Protein Mutant With Gly 134; D-Ribose-Binding Dehydrogena: D-Glyceraldehyde-3-Phosphate Dehydroge Protein Mutant With Ile 132: Drosophila Neuroglian; Dtdp nase, D-Glyceraldehyde-3-Phosphate-Dehydrogena; 4-Dehydrorhamnose 3.5-Epimerase: Dtdp-4-Dehydrorham D-Glyceraldehyde-3-Phosphate-Dehydrogenase; Dhps, nose Reductase, Rfbd O: Dtdp-6-Deoxy-D-Xylo-4-Hexylose Dihydropteroate Synthase: D-Hydantoinase; Diacylglycerol 3.5-Epimerase: Dtdp-D-Glucose 4,6-Dehydratase; Dtdp kinase; Diadenosine Tetraphosphate Hydrolase; Diamine Glucose Oxidoreductase: Dual Adaptor Of Phosphotyrosine acetyltransferase 1; Diamine acetyltransferase 2: Diami and 3-Phosp: Dual Specificity Mitogen-Activated Protein K: nopimelate Decarboxylase; Dianthin 30; Dienelactone Dual Specificity Protein Kinase Clk1; Duck Ovotransferrin; Hydrolase; Dienoyl-Coa Isomerase; Diga16: Di-Haem Cyto Duodenase; Dutp Pyrophosphatase: D-Xylose Isomerase: E. chrome C Peroxidase; Diheme Cytochrome C Napb: Di coli citrate synthetase; E. coli glutathione reductase; E. coli Heme Peroxidase; Dihydrodipicolinate Reductase; Dihy malate dehydrogenase; E. Coli Maltodextrin Phosphorylase; drodipicolinate Reductase; Dihydrodipicolinate Synthase: E. coli pyruvate dehydrogenase; E. coli ribosomal proteins; Dihydrofolate Reductase; Dihydrofolate Reductase (ma Eafp 2: Early Endosomal Autoantigen 1: Ecotin: Eh Domain larial); Dihydrolipoamide Dehydrogenase; Dihydrolipoyl Binding Protein Epsin; Eif2Gamma; Elastase; Elastase 1: dehydrogenase, mitochondrial precursor, Dihydrolipoyl Eledoisin; Elongation Factor: Elongation Factor 1-Alpha; Transacetylase; Dihydrolipoyllysine-residue acetyltrans Elongation Factor 2: Elongation Factor G; Elongation Factor ferase component of pyruvate dehydrogenase complex, mito G Complexed With Guanosine; Elongation Factor Tu; Endo/ chondrial precursor; Dihydroneopterin Aldolase; Dihydro Exocellulase E4, Endo-1,4-B-D-Mannanase; Endo-1,4-Beta orotase; Dihydroorotate Dehydrogenase; Dihydroorotate Glucanase Engf; Endo-1,4-Beta-D-Xylanase; Endo-1,4- Dehydrogenase A; Dihydroorotate Dehydrogenase, mito Beta-Glucanase; Endo-1,4-Beta-Glucanase F. Endo-1,4- chondrial Precursor: dihydropterate synthase (bacterial); Beta-Xylanase; Endo-1,4-beta-Xylanase 2 precursor, Endo Dihydropteridine Reductase: Dihydropteridine Reductase: 1,4-Beta-Xylanase A: Endo-1,4-Beta-Xylanase A Precursor: Dihydropteroate synthase: Dihydropteroate Synthase (ma Endo-1,4-Beta-Xylanase II: Endo-1,4-Beta-Xylanase Y: larial); Dihydropteroate synthase (Pneumocystis carinii); Endo-Alpha-Sialidase; Endo-Beta-1,4-Glucanase; Endo Dihydropteroate Synthase I: Dihydropyridine calcium chan Beta-N-Acetylglucosaminidase F3; Endocellulase E 1: Endo nel; Dihydropyridine-sensitive L-type, calcium channel glucanase; Endoglucanase 5A: Endoglucanase 9G. Endoglu alpha-2/ delta Subunits; Dihydropyrimidine dehydrogenase; canase A: Endoglucanase B; Endoglucanase C. Dihydroxyacetone Kinase; Diisopropylfluorophosphatase; Endoglucanase I: Endoglucanase I: Endoglucanase V Cello Dimeric Hemoglobin: Dimethyl Sulfoxide Reductase: biose Complex: Endoplasmic Reticulum Mannosyl-Oli Dipeptidyl Aminopeptidase-Like Protein 6: Dipeptidyl Pep gosacchari; Endoplasmin, Endopolygalacturonase; Endopo tidase I Dipeptidyl Peptidase IV: Dipeptidyl Peptidase IV: lygalacturonase; EndoSome-Associated Protein, Endothelial Dipeptidyl Peptidase IV Soluble Form; Diphtheria Toxin; Nitric-Oxide Synthase: Endothelial Protein C Receptor; Diphtheria Toxin Repressor; Diphthine Synthase: Dissimila Endothelin B receptor precursor; Endothelin-1; Endothelin-1 tory Copper-Containing Nitrite: Dissimilatory Copper-Con receptor precursor, Endothiapepsin, Endothiapepsin precur taining Nitrite Redu; D-lactate dehydrogenase: D-Lactate sor; Endoxylanase; Endoxylanase 1 1A: Engrailed Home Dehydrogenase; Dlp-1: D-Maltodextrin-Binding Protein; odomain; Enhancing Lycopene Biosynthesis Protein; Dmso Reductase; DNA Adenine Methylase; DNA Beta-Glu Enkephalinase; Enolase; Enolase 1: Enoyl Acp Reductase: cosyltranferase: DNA Cytosine Methyltransferase Dnmt2: Enoyl Acyl Carrier Protein Reductase; Enoyl-Acyl-Carrier DNA Double-Strand Break Repair RadS0 Atpase; DNA Protein Reductase: Enoyl-Acyl-Carrier-Protein Reduc Gyrase B; DNA gyrase subunit A; DNA Gyrase Subunit B; tase; Enoyl-Acyl-Carrier-Protein Reductase: Enoyl-Acyl DNA Helicase; DNA Ligase; DNA Ligase I: DNA Ligase III; Carrier-Protein Reductase Nadh: Enoyl-acyl-carrier-pro DNA Ligase, Nad-Dependent; DNA Ligase, Nad-Depen tein reductase NADH: Enoyl-Acp Reductase: Enoyl-Acp dent; DNA Mismatch Repair Protein Mutl; DNA Nucleotide Reductase: Enoyl-Acyl Carrier Protein: Enoyl-Coa Excision Repair Enzyme Uvrb; DNA Photolyase; DNA Poly Hydratase: Enoyl-Coa Hydratase, Mitochondrial; Envelope merase; DNA Polymerase (human cytomegalovirus); DNA Glycoprotein; Envelope Glycoprotein; Envelope glycopro polymerase (human herpes simplex virus 1); DNA Poly tein GP340; Envelope glycoprotein GP340/GP220; Eosino merase (human); DNA polymerase (Varicella-zoster virus); phil Cationic Protein; Eosinophil Lysophospholipase Chain: DNA Polymerase alpha (human); DNA Polymerase Beta; A: Eosinophil-Derived Neurotoxin; Ep-Cadherin; Ephrin DNA Polymerase I: DNA Polymerase III Subunit Gamma; Type-A Receptor 2; Ephrin-A5; Ephrin-B2: Epidermal DNA Polymerase III, Epsilon Chain; DNA Primase; DNA Growth Factor: Epidermal Growth Factor Receptor; Epider Primase Small Subunit; DNA Primase/Helicase; DNA Repair mal Growth Factor Receptor 2: Epidermal growth factor US 2008/0220441 A1 Sep. 11, 2008 47 receptor precursor: Epidermin Modifying Enzyme Epid; Epi Hormone Receptor; Follistatin: Folylpolyglutamate syn didymal Secretory Protein E1 Epilancin 15X; Epoxide thase; Folylpolyglutamate synthase, mitochondrial; Hydrolase: Epoxide Hydrolase 2, Cytoplasmic; Epsin; Epsp Folylpolyglutamate Synthetase: Formaldehyde Dehydroge Synthase: Ergosterol biosynthetic protein 28; Ermc' Methyl nase; Formaldehyde Ferredoxin Oxidoreductase: Formalde transferase; Erv2 Protein, Mitochondrial; Erythrina Crista hyde-Activating Enzyme Fae; Formate Acetyltransferase 1: Galli Lectin; Erythropoietin receptor, Esal Histone Acetyl Formate Dehydrogenase H; Formiminotransferase-Cy transferase; Esal Protein: E-Selectin; Esta; Esterase; clodeaminase; Formyl-Coenzyme A Transferase; Formylme Estradiol 17 Beta-Dehydrogenase 1: Estradiol 17 Beta-De thionine Deformylase: Four-Helix Bundle Model; Fpra; Fr-1 hydrogenase 4: Estradiol 17-beta-dehydrogenase 1: Estradiol Protein; Fragile Histidine Protein; Fragile Histidine Triad 17-beta-dehydrogenase 2: Estradiol 17-beta-dehydrogenase Protein; Fructan 1-Exohydrolase Iia; Fructose 1,6-Bisphos 3: Estradiol 17-beta-dehydrogenase 8: Estrogen Receptor; phatase. Fructose 1,6-Bisphosphatase/Inositol Monopho: Estrogen Receptor (ER); Estrogen Receptor Alpha; Estrogen Fructose 1,6-Bisphosphate Aldolase; Fructose-1,6-Bis; Fruc Receptor Beta: Estrogen Sulfotransferase; Estrogen-Related tose-1,6-Bisphosphatase; Fructose-2,6-Bisphosphatase; Receptor Gamma; Eukaryotic Peptide Chain Release Factor Fructose-Bisphosphate Aldolase; Fructose-Bisphosphate GTP-, Eukaryotic Translation Initiation Factor 4E: Evolved Aldolase A. Fructose-Bisphosphate Aldolase Class I; Fruc beta-galactosidase alpha-Subunit; Excinuclease Abc Subunit tose-Bisphosphate Aldolase II; FtsZ. Fucose-Specific Lectin; B; Exo-; Exocellobiohydrolase I: Exoglucanase I: Exo-Inuli Fumarase C; Fumarate Hydratase Class II; Fumarate reduc nase; Exo-Maltotetraohydrolase; Exopolyphosphatase; Exo tase flavoprotein subunit; Fumarylacetoacetate Hydrolase; toxin A: Expressed Protein; Exterior Membrane Glycopro Fusion Protein; Fusion Protein Consisting Of Kinesin-Like tein Gp120; Extracellular calcium-sensing receptor Pr; Fusion Protein Consisting Of Staphylococcus: Fv Frag precursor: Extracellular Regulated Kinase 2: Extracellular ment; G Protein Gi Alpha 1: G15-Gramicidin A; G25K GTP Signal-Regulated Kinase 2: Extracellular Subtilisin-Like Binding Protein; GABA Transaminase; GABA-A Receptor; Serine Protein: Extrahepatic lipoprotein lipase (LL); F17-Ag GABA-B Receptor; Gag Polyprotein; Gall0 Bifunctional Lectin; F1-Gramicidin A; F1-Gramicidin C: F420-Depen Protein; Galactanase; Galactokinase; Galactose Mutarotase; dent Alcohol Dehydrogenase; F65A/Y131C-Mi Carbonic Galactose Oxidase; Galactose Oxidase Precursor; Galactose Anhydrase V: Factor D: Factor IIIFactor IX Factor VIIIFactor 1-Phosphate Uridyl Transferase-Lik; Galactose-1-Phosphate X; Factor Inhibiting Hifl; Farnesyl Diphosphate Synthase: Uridylyltransferase; Galactose-Binding Protein Complex Farnesyl pyrophosphate synthetase; Fasciclin I; Fatty Acid With Gluco; Galactose-Specific Lectin; Galactoside Binding Protein: Fatty Acid Binding Protein Homolog: Fatty O-Acetyltransferase; Galactosylgalactosylxylosylprotein Acid Metabolism Regulator Protein; Fatty Acid/Phospho 3-Beta-G: Galectin-1; Galectin-1; Galectin-2: Galectin-3, lipid Synthesis Protei: Fatty Acid-Binding Protein; Fatty Galectin-3; Galectin-7: Gamma Chymotrypsin; Gamma Acid-Binding Protein, Adipocyte; Fatty Acid-Binding Pro Aminobutyrate Metabolism Dehydratase/I: Gamma-ami tein, Brain; Fatty acid-binding protein, liver; Fatty aldehyde nobutyric-acid receptor alpha-2 Subunit precursor; Gamma dehydrogenase; Fatty-Acid Amide Hydrolase. F-Box Only aminobutyric-acid receptor alpha-3 Subunit precursor; Protein 2: Fc Fragment; Fc Gamma Receptor FCGR1 HU Gamma-aminobutyric-acid receptor alpha-4 Subunit precur MAN: Feglymycin; Feline Immunodeficiency Virus Pro sor; Gamma-aminobutyric-acid receptor alpha-5 Subunit pre tease: Feline Leukemia Virus Receptor-Binding Domai; cursor; Gamma-aminobutyric-acid receptor alpha-6 Subunit Ferredoxin; Ferredoxin II; Ferredoxin Reductase; Ferre precursor; Gamma-aminobutyric-acid receptorrho-1 Subunit doxin: Nadp+ Oxidoreductase: Ferredoxin: Nadp+ Reduc Precursor: Gamma-Glutamyl Hydrolase; Ganglioside Gm2 tase; Ferredoxin-Dependent Glutamate Synthase: Ferre Activator; Gastrotropin; GDH/6PGL endoplasmic bifunc doxin-Nadp Reductase: Ferredoxin-Nadip Reductase: tional protein precursor Includes: Glucose 1-dehydroge Ferredoxin-Nadp+ Reductase: Ferredoxin-Nadp+ Reduc nase; Gdnf Family Receptor Alpha 1: GDP-D-Mannose-4,6- tase; Ferric Hydroxamate Receptor; Ferric Hydroxamate Dehydratase; GDP-Fucose Synthetase; GDP-L-fucose Uptake Receptor; Ferrichrome-Binding Periplasmic Protein; synthetase; GDP-Mannose 4.6 Dehydratase; GDP-Mannose Ferrichrome-Iron Receptor; Ferrichrome-Iron Receptor Pre 4,6-Dehydratase; GDP-Mannose 6-Dehydrogenase; GDP cursor; Ferripyochelin Binding Protein: Ferripyoverdine Mannose Mannosyl Hydrolase; General Control Protein Receptor, Ferritin heavy chain; Ferritin light chain; Ferroche Gcn4; General Secretion Pathway Protein E: General Stress latase: Feruloyl Esterase A; Fez-1 Beta-Lactamase; Fgf Protein 69; Genome Polyprotein; Gephyrin; Geranyltran Receptor 1: Fiber Protein: Fibrin; Fibrinogen-420; Fibroblast stransferase; Gfp-Like Chromoprotein Fp595; Gial; Giding Activation Protein, Alpha Subunit; Fibroblast Growth Factor Protein-Mglb: Glandular Kallikrein-13; Glcnac1P Uridyl 9; Fibroblast Growth Factor Receptor 2: Fibroblast growth transferase Isoform 1: Agx1; Globin; Globin I; Globin Li637; factor-4 precursor: Fibronectin; Fimbrial Lectin; Fk506 Globin-3; Glpe Protein; Glucagon receptor; Glucan 1,3-Beta Binding Protein: Fk506-Binding Protein: FK506-binding Glucosidase I/II: Glucan 1,4-Alpha-Maltohexaosidase; Glu protein 1A: Fk506-Binding Protein 4; Fkbp 12.6; FKBP12 carate Dehydratase; Glucoamylase; Glucoamylase-471; Glu rapamycin complex-associated protein; Fkbp25: Fkbp-Type cocorticoid Receptor, Glucokinase; Glucokinase Isoform 2: Peptidyl-Prolyl Cis-Trans Isom; Fksg76; FL cytokine recep Gluconate 5-Dehydrogenase; Gluconate Kinase; Glu tor precursor: Flavin reductase: Flavocytochrome B2: Flav cosamine 6-Phosphate Synthase; Glucosamine-6-Phosphate ocytochrome C: Flavocytochrome C Fumarate Reductase: Deaminase; Glucosamine-6-Phosphate Isomerase: Glu Flavocytochrome C3; Flavocytochrome C3 Fumarate Reduc cosamine-Fructose-6-Phosphate Aminotrans; Glucosamine tase: Flavodoxin; Flavodoxin Reductase: Flavohemoprotein; Phosphate N-Acetyltransferase: Glucose 1-Dehydrogenase; Flavoprotein; Fluorescent Protein Fp538; Fmn-Binding Pro Glucose 6-Phosphate 1-Dehydrogenase; Glucose 6-Phos tein; Fms 1 Protein; Focal Adhesion Kinase 1: Folate receptor phate 1-Dehydrogenase; Glucose 6-Phosphate Dehydroge alpha; Folate receptor beta; Folate receptor gamma; Folate nase; Glucose Dehydrogenase; Glucose Oxidase; Glucose-1- transporter 1: Folc Bifunctional Protein; Follicle Stimulating Phosphatase: Glucose-1-Phosphate Adenylyltransferase US 2008/0220441 A1 Sep. 11, 2008 48

SmaI: Glucose-1-Phosphate Cytidylyltransferase: Glucose formyltransferase (fragment); Glycinamide Ribonucleotide 1-Phosphate Thymidylyltransferas; Glucose-1-Phosphate Transformylase; GLycine alpha 2 receptor, Glycine amidi Thymidylyltransferase: Glucose-6-Phosphate 1-Dehydroge notransferase; Glycine Betaine-Binding Periplasmic Protein; nase; Glucose-6-Phosphate Isomerase: Glucose-Fructose Glycine dehydrogenase; Glycine N-Methyltransferase: Gly Oxidoreductase; Glucose-Fructose Oxidoreductase; Glu cine Oxidase; Glycine receptor alpha-1 chain Precursor: cose-Resistance Amylase Regulator, Glucosylceramidase; Glycine receptor alpha-3 chain; Glycine receptor beta chain; Glucuronyltransferase I: Glutaconyl-Coa Decarboxylase A Glycogen phosphorylase; Glycogen Phosphorylase b: Gly Subunit; Glutamate NMDA receptor subunit epsilon 1 pre cogen Phosphorylase, Liver Form; Glycogen phosphorylase, cursor; Glutamate NMDA receptor subunit epsilon 2 pre muscle form; Glycogen Synthase 1: Glycogen Synthase cursor; Glutamate NMDA receptor subunit epsilon 3 pre Kinase-3 Beta; Glycogenin-1; Glycolate Oxidase; Glycolipid cursor; Glutamate Carboxypeptidase II: Glutamate 2-Alpha-Mannosyltransferase: Glycolipid Transfer Protein; decarboxylase 1: Glutamate decarboxylase 2: Glutamate Glycoprotein D: Glycoprotein-Fucosylgalactoside Alpha Decarboxylase Alpha; Glutamate Decarboxylase Beta; Galac; Glycoprotein-Fucosylgalactoside Alpha-N-Ace; Gly Glutamate Dehydrogenase; Glutamate Dehydrogenase; cosyl Transferase: Glycosylase; Glycosyltransferase A: Gly Glutamate Dehydrogenase 1: Glutamate dehydrogenase 1, cosyltransferase B; Glycosyltransferase Gtfa; mitochondrial precursor; Glutamate dehydrogenase 2, mito Glycosyltransferase Gitfl; Glyoxalase Family Protein; Gly chondrial precursor, Glutamate Racemase; Glutamate recep oxalase II: Glyoxylate reductase/hydroxypyruvate reductase; tor 1 Precursor: Glutamate Receptor 2: Glutamate Receptor Gmp Reductase I: GMP synthase glutamine-hydrolyzing: 2 Precursor; Glutamate receptor 3: Glutamate receptor 4: Gmp Synthetase; Gomesin; Gonadotropin-releasing hor Glutamate Receptor 6: Glutamate Receptor Subunit 2: mone II receptor; Gonadotropin-releasing hormone receptor; Glutamate Receptor, Ionotropic Kainate 1: Glutamate recep GP41 envelope protein (first heptad repeat); Gp70; GPIIb tor, ionotropic kainate 1 precursor; Glutamate Receptor, Receptor; GPIIIa Receptor; Gramicidin; Gramicidin A; Ionotropic Kainate 2: Glutamate receptor, ionotropic kainate Gramicidin B; Gramicidin C; Gramicidin D: Gramicidin 3: Glutamate receptor, ionotropic kainate 5: Glutamate Semi Synthetase 1: Granulocyte colony stimulating factor receptor aldehyde Aminotransferase; Glutamate-Cysteine Ligase; (CD114 antigen); Granulocyte-macrophage colony Stimulat Glutamate-cysteine ligase catalytic subunit: Glutamate-cys ing factor receptor (GM-CSF-R-alpha or CSF2R); Granul teine ligase regulatory Subunit; Glutaminase, kidney isoform; ysin; Granzyme B; Green Fluorescent Protein; Green-Fluo Glutaminase, liver isoform; Glutaminase-Asparaginase; rescent Protein; Griffonia Simplicifolia Lectin 4: Group X Glutamine Aminotransferase: Glutamine Phosphoribosylpy Secretory Phospholipase A2: Growth Differentiation Factor rophosphate: Glutamine Phosphoribosylpyrophosphate Ami 5: Growth Factor Receptor-Bound Protein 2: Growth hor dot; Glutamine Receptor 2: Glutamine Synthetase: mone releasing hormone receptor (GRF receptor); Growth Glutamyl-Endopeptidase; Glutamyl-tRNA Reductase: arrest-specific protein 6: Grp 1: Gst2 Gene Product; GTP Glutamyl-tRNA Synthetase: Glutaredoxin 3: Glutaryl-Coa Cyclohydrolase I: Gtpase-Activating Protein 1: GTP-Bind Dehydrogenase; Glutathine Synthetase; Glutathione Reduc ing Nuclear Protein Ran; GTP-Binding Protein Ran; GTP tase; Glutathione reductase (mitochondrial); Glutathione Binding Protein Rheb; GTP-Binding Protein YptS1; GTP S-Transferase; Glutathione S-Transferase; Glutathione Binding Protein Ypt7P; GTP-Binding Protein Ysxc: S-Transferase 1-6: Glutathione S-Transferase 2: Glutathione Guanidinoacetate Methyltransferase; Guanidinoacetate S-Transferase 26 Kda; Glutathione S-Transferase Al; Glu N-Methyltransferase; Guanine Deaminase; Guanine Nucle tathione S-Transferase A1-1; Glutathione S-Transferase otide Exchange Factor and I; Guanine Nucleotide Exchange A3-3; Glutathione S-Transferase Class Pi Chimaera; Glu Factor and Integ; Guanine Nucleotide-Binding Protein G: tathione S-Transferase Gita-1A; Glutathione S-Transferase Guanine Phosphoribosyltransferase; Guanylate Kinase; Gua Mu 1. Glutathione S-Transferase Mu 2: Glutathione S-Trans nyl-Specific Ribonuclease T1: Guanyl-Specific Ribonu ferase P. Glutathione S-transferase pi; Glutathione S-Trans clease T1 Precursor; Gurmarin; H-. H. Pylorirdx A: H+/K+ ferase Tsi-1, Glutathione S-Transferase Ya Chain; Glu ATPase (Proton pump); Ha1; Haematopoetic Cell Kinase; tathione S-Transferase Yb 1: Glutathione S-Transferase Yfyf: Haloalkane Dehalogenase; Halohydrin Dehalogenase; Glutathione S-Transferase, Mitochondrial; Glutathione Syn Halorhodopsin; Halotolerance Protein Ha12; Halotolerance thetase; Glutathione Transferase; Glutathione Transferase; Protein Hal 3: Hev NS5B Polymerase: Heys Beta3-Cys Ana Glutathione Transferase Gst 1-3. Glutathione Transferase logue Of Hiv Gp41; Halp; Head Decoration Protein: Heat Gst1-6: Glutathione Transferase Zeta; Glutathione-Depen Shock 70 Kda Protein 1: Heat Shock 90 Kda Protein 1, Alpha; dent Formaldehyde Dehydroge: Glutathione-Dependent Heat Shock Cognate Kda70; Heat Shock Locus U; Heat Formaldehyde-Activatin: Glutathione-Requiring Prostaglan Shock Protein 90; Heat Shock Protein Hslu; Heat Shock din D Syntha; Glutathione-S-Transferase; Glyceraldehyde Protein Hsp90-Alpha; Heat Shock Protein Hsp90-Beta; Heat 3-Phosphate Dehydrogenase; Glyceraldehyde 3-Phosphate Shock Protein Hsp33; Heat Shock Transcription Factor; Heat Dehydrogenase; Glyceraldehyde 3-Phosphate Dehydroge Shock-Like Protein 1: Heat-labile enterotoxin B chain pre nase A; Glyceraldehyde-3-Phosphate Dehydrogenase; Glyc cursor; Heat-Labile Enterotoxin B Subunit; Heat-Shock 70 eraldehyde-3-Phosphate Dehydrogenase; Glyceraldehyde-3- Kd Protein; Heat-Shock Cognate 70 Kd Protein: Heavy Phosphate Dehydrogenase A: Glyceraldehyde-3-phosphate chain; Heavy chain 1 B72.3 (murine); Hemagglutinin Precur dehydrogenase, liver; Glyceraldehyde-3-phosphate dehydro Sor, Hemagglutinin-Neuraminidase; Hemagglutinin genase, testis-specific; Glycerol Dehydratase; Glycerol Neuraminidase Glycoprotein; Hematopoetic Cell Kinase Dehydrogenase; Glycerol Kinase; Glycerol Uptake Facilita Hck; Hematopoietic Prostagladin D Synthase: Heme Oxyge tor Protein; Glycerol Uptake Operon Antiterminator-Re: nase; Heme Oxygenase 1; Heme Oxygenase 2: Heme Oxy Glycerol-3-Phosphate Cytidylyltransferase; Glycerol-3- genase-1; Heme Pas Sensor Protein: Heme-Based Aerotactic Phosphate Dehydrogenase; Glycerol-3-phosphate dehydro Transducer Hemat; Heme-Based Methyl-Accepting Chemo genase NAD+, cytoplasmic; Glycinamide ribonucleotide taxis P: Heme-Based Methyl-Accepting Chemotaxis Prote: US 2008/0220441 A1 Sep. 11, 2008 49

Heme-Binding Protein A: Hemerythrin; Hemk Protein; ase; Hydrogen peroxide-inducible genes activator; Hydro Hemo: Hemocyanin; Hemocyanin; Hemoglobin: Hemoglo lase; Hydrolase Angiogenin; Hydroxyacid Oxidase 3: bin beta chain; Hemoglobin Gamma Chains; Hemoglobin V: Hydroxyacylglutathione Hydrolase; Hydroxyethylthiazole Hemoglobin-Like Protein Hbn: Hemoglobin-Like Protein Kinase; Hydroxylamine Oxidoreductase; Hydroxylamine Hbo: Hemolytic Lectin Cel-III: Hemolytic Lectin Lsla: Reductase: Hydroxymethylglutaryl-CoA lyase; Hydroxyni Hemopexin; Heparan Sulfate; Heparan Sulfate D-Glu trile Lyase, Hydroxyquinol 1,2-Dioxygenase; Hydroxys cosaminyl 3-O-Sulfotra: Heparan Sulfate N-Deacetylase/N- teroid Sulfotransferase: Hypothetical 22.5 Kda Protein. In Sulfotransfe; Heparin Binding Protein; Heparin Cofactor II; Tub1-Cp; Hypothetical 22.5 Kda Protein. In Tub1-Cpr3 I: Heparin cofactor II precursor; Heparin-Binding Growth Fac Hypothetical 28.8 Kda Protein In Psd1-Sk: Hypothetical 32.1 tor 1; Heparin-binding growth factor 1 precursor; Heparin Kda Protein. In Adha-Rcal I: Hypothetical 65.0 Kda Protein Binding Protein: Hepatitis C Virus Ns5B RNA Polymerase: In Cox 14-C: Hypothetical 65.0 Kda Protein In Cox 14-Cos3; Hepatitis C Virus Ns5B RNA-Dependent RNA Pol; Hepato Hypothetical Abc Transporter ATP-Binding; Hypothetical cyte Growth Factor; Hepatocyte Growth Factor Activator Pre Abc Transporter ATP-Binding Pro; Hypothetical Isochoris cursor; Hepatocyte Growth Factor Receptor; Hepatocyte matase Family Protein: Hypothetical Oxidoreductase Yahf: Growth Factor-Regulated Tyrosine; Hepatocyte Nuclear Fac Hypothetical Oxidoreductase Yiak; Hypothetical Oxi tor 1-Alpha; Hepatocyte Nuclear Factor 4-Alpha; Hepatocyte doreductase Yghd; Hypothetical Protein: Hypothetical Pro Nuclear Factor 4-Gamma; Her-1 Protein; Heroin Esterase; tein Af0103: Hypothetical Protein Af1403; Hypothetical Pro Herpes Thymidine Kinase; Hevamine: Hevamine A: Hevea tein Af1521: Hypothetical Protein Af1796: Hypothetical brasiliensis; Hevein; Hevein: Hexokinase; Hexokinase Type Protein Af2198: Hypothetical Protein Agr L 1239; Hypo I: Hexon Protein: Hexose-1-Phosphate Uridylyltransferase: thetical Protein Alriš027; Hypothetical Protein Apc35924; Hi0065; Hil317; High Affinity Immunoglobulin Epsilon Hypothetical Protein Apc36103: Hypothetical Protein Recepto: High affinity immunoglobulin epsilon receptor Aq 328: Hypothetical Protein Bsu33890: Hypothetical Pro alpha-Subunit precursor, High affinity immunoglobulin epsi tein EgcO68; Hypothetical Protein Fli11149; Hypothetical lon receptor gamma-Subunit precursor, High Affinity Ribose Protein HiO828: Hypothetical Protein Hil388.1: Hypotheti Transport Protein Rbsd; High Mobility Group Protein 1: cal Protein Lech: Hypothetical Protein Mds018: Hypotheti High-Affinity Branched Chain Amino Acid Tran; High-Af cal Protein M1247; Hypothetical Protein PaO094; Hypo finity Branched-Chain Amino Acid Tran; High-affinity thetical Protein Pa2260: Hypothetical Protein Pa3270; cAMP-specific 3',5'-cyclic phosphodiesterase 7A: High-af Hypothetical Protein Pa3967: Hypothetical Protein Pa-Ho: finity cationic amino acid transporter-1; High-affinity choline Hypothetical Protein pH0236: Hypothetical Protein pH0642: transporter 1; High-Molecular-Weight Cytochrome C. Hista Hypothetical Protein pH1313; Hypothetical Protein pH1602; mine H1 Receptor; Histamine H2 Receptor; Histamine H4 Hypothetical Protein pH1897: Hypothetical Protein pH1917: Receptor. Histamine N-Methyltransferase: Histidine ammo Hypothetical Protein Rbstp0775: Hypothetical Protein nia-lyase. Histidine Containing Protein; Histidine decar Rv0793; Hypothetical Protein RV0819; Hypothetical Protein boxylase: Histidine Triad Nucleotide-Binding Protein: Histi Rv1170; Hypothetical Protein Rv1347C/Mt1389: Hypotheti dine triad nucleotide-binding protein 1: Histidinol cal Protein Rv2238C/Mt2298: Hypothetical Protein Rv2991; Dehydrogenase. Histidinol Phosphate Aminotransferase: Hypothetical Protein Slr1257: Hypothetical Protein Smu. Histidinol-Phosphate Aminotransferase: Histidyl-tRNA syn 260: Hypothetical Protein Sso2532: Hypothetical Protein thetase: Histo-Blood Group Abo System Transferase: His Ta0175: Hypothetical Protein Tal320: Hypothetical Protein tone Acetyltransferase Gcn5; Histone Deacetylase 8: Histone Tm()021: Hypothetical Protein Tm()449; Hypothetical Pro H3; Histone Methyltransferase Dot1L: Histone-Lysine tein Tm1070; Hypothetical Protein Tm1380: Hypothetical N-Methyltransferase, H3 Lysin; Hiv 1 Gp41 Hser Analogue Protein Tm 1457: Hypothetical Protein Tm 1553: Hypotheti Peptide Ace-Ile-T: Hiv-1 Integrase: Hiv-1 Protease; HIV-1 cal Protein Tm 1643; Hypothetical Protein Tm841; Hypo Reverse Transcriptase; HIV-2 Protease; Hmg-Coa Reduc thetical Protein Tt0907: Hypothetical Protein Tt 1426; Hypo tase; Holliday Junction DNA Helicase Ruvb; Holliday-Junc thetical Protein Vc1899: Hypothetical Protein Vca0042: tion Resolvase: Holo-; Holo-D-Glyceraldehyde-3-Phosphate Hypothetical Protein Ycdx: Hypothetical Protein Ycfc: Dehydrogen; Homo Sapiens V-Kit Hardy-Zuckerman 4 Hypothetical Protein Ydce: Hypothetical Protein Yddu: Feline; Homoprotocatechuate 2,3-Dioxygenase; Hypothetical Protein Yese: Hypothetical Protein Yfdw: Homoserine Dehydrogenase; Homoserine Kinase; Hormone Hypothetical Protein Ygbm; Hypothetical Protein Yhai; Receptor Alpha 1. Thra1; Horseradish Peroxidase C1A: Host Hypothetical Protein Yhda: Hypothetical Protein Yhfp: Factor For Q Beta; Hpha; H-Protein; HpV11 Regulatory Pro Hypothetical Protein, Similar To Potassium C. Hypothetical tein E2: Hst2 Protein: HTH-type transcriptional regulator Protein, Similar To Strepto: Hypothetical Shikimate 5-Dehy malT: Htlv-1 Gp21 Ectodomain/Maltose-Binding Prote: drogenase-L; Hypothetical Transcriptional Regulator I; Human Beta2-Glycoprotein I; Human Cd2; Human Cyto Hypothetical Transcriptional Regulator In Qa: Hypothetical chrome P450 CYP2D6; Human Cytochrome P450 CYP3A4; tRNA/Rrna Methyltransferase Hi0: Hypothetical Upf)124 Human Growth Hormone Receptor; Human Immunodefi Protein Yfilh; Hypothetical Upfol31 Protein pH0828: Hypo ciency Virus Type 2: Human keratinocyte growth factor thetical Upfo204 Protein Af0625; Hypothetical Zinc-Type receptor; Human Neutrophil Gelatinase: Human Ornithine Alcohol Dehydrogenase; Hypoxanthine Phosphoribosyl Decarboxylase; Human Procathepsin L. Human Protective transferase: Hypoxanthine-Guanine Phosphoribosyltrans Protein Human RSV Fusion glycoprotein; Human Sigma fera; Hypoxanthine-Guanine Phosphoribosyltransfera; Alcohol Dehydrogenase; Human Sorbitol Dehydrogenase; hypoxanthine-guanine phosphoribosyltransferase; Hypox Human Thioltransferase: Human Thioredoxin Peroxidase-B; anthine-Guanine-Xanthine Phosphoribosyl: lag-Nucleoside Hut Operon Positive Regulatory Protein: Hyaluronate Lyase: Hydrolase; Iclr Transcriptional Regulator, Ig Gamma-1 Hyaluronate lyase precursor, Hyaluronidase; Hyaluronoglu Chain C Region; Ig Gamma-2A Chain C Region, Ig kappa cosaminidase: Hybrid; Hybrid Cluster Protein: Hydantoin chain V-III region GOL: IgA2: Igf-1 Receptor Kinase; IGG1; US 2008/0220441 A1 Sep. 11, 2008 50

II Purple Acid Phosphatase: II-6 Receptor Alpha Chain; Ileal Heavy Chain; Kinesin Heavy Chain-Like Protein; Kinesin Lipid Binding Protein: Imaginal Disc Growth Factor-2: Imi Motor Ncd; Kinesin-Like Protein Kar3; Kinesin-Like Protein dazole Glycerol Phosphate Dehydratase: Imidazole Glycerol Kifl 1; Kinesin-Like Protein Kifl A: Kinesin-Like Protein Phosphate Synthase Hishf Immunoglobulin Alpha Fc Kif2C; Kinesin-Related Motor Protein Eg5; Kynureninase; Receptor Immunoglobulin Heavy Chain Epsilon-1. Immuno Kynurenine/alpha-aminoadipate aminotransferase mito globulin Lambda Light Chain; Immunoglobulin Lambda chondrial; Kynurenine-Oxoglutarate Transaminase I, L., L-2- Light Chain Dimer, Immunoglobulin Vh Domain; Immuno Haloacid Dehalogenase; L-2-Hydroxyisocaproate Dehydro globulin VI Domain: IMP dehydrogenase: Imp-1 Metallo genase; L-3-Hydroxyacyl Coa Dehydrogenase; L-3- Beta-Lactamase; Indole-3-Glycerol Phosphate Synthase: Hydroxyacyl-Coa Dehydrogenase; L-3-Phosphoserine Indole-3-Glycerol-Phosphate Synthase; Indole-3-Pyruvate Phosphatase; Laccase; Laccase; Laccase 1: Laccase 2: Lac Decarboxylase; Indoleamine 2,3-dioxygenase; Inducible tadherin: Lactaldehyde Reductase; Lactate Dehydrogenase; Nitric Oxide Synthase; Influenza A Subtype N2 Neuramini Lactate Dehydrogenase; Lactoferrin, Lactoferrin; Lactose dase; Influenza A Subtype N9 Neuraminidase; Influenza Permease; Lactotransferrin; Lactoylglutathione Lyase; Virus B/Lee/40 Neuraminidase; Inorganic Polyphosphate/ L-Alanine Dehydrogenase; L-Allo-Threonine Aldolase; ATP-Glucomannokinase; Inorganic Polyphosphate/ATP Lambda Exonuclease; Laminarinase 16A: L-Amino Acid Nad Kinase; Inorganic Pyrophosphatase; Inosine Monophos Oxidase; Lanosterol Synthase; Lantibiotic Mersacidin; phate Dehydrogenase 2: Inosine Monophosphate L-Arabinose-Binding Protein: L-Arabinose-Binding Protein Dehydrogenase I: Inosine-5'-Monophosphate Dehydroge Complex With L-A; Large T Antigen; L-Arginine: Glycine nase; Inosine-5'-Monophosphate Dehydrogenase 2: Inosine Amidinotransferase; L-Arginine\: Glycine Amidinotrans Adenosine-Guanosine Preferring Nucle; Inosine-Adenosine ferase; L-Asparaginase; L-Asparagine Amidohydrolase; Guanosine-Preferring Nucle; Inositol 1,3,4-Trisphosphate L-Aspartate Ammonia-Lyase; L-Aspartate Oxidase; Lck 5/6-Kinase; Inositol 1,4,5-Trisphosphate Receptor Type 1: Kinase; L-Cysteine/L-Cystine C-S Lyase; Lectin; Lectin; Inositol Monophosphatase; Inositol-3-Phosphate Synthase: Lectin Cel-1, N-Acetyl-D-Galactosamine-Speci; Lectin Inositol-3-Phosphate Synthase; Inositol-Trisphosphate 3-Ki Complex With Lactose; Lectin Pal; Lectin, Isoform 1: Lectin nase A, Insecticyanin A Form: Insulin; Insulin receptor, Insu D2: Leghemoglobin: Leghemoglobin A; Lens Fiber Major lin-Like Growth Factor I; Insulin-Like Growth Factor Recep Intrinsic Protein; Lethal; Lethal Factor; Leucine Aminopep tor 1: Intact Lactose Operon Repressor With Gratuit; tidase; Leucine carboxyl methyltransferase 1: Leucine car Integrase; Integrin alpha-4: Integrin Alpha-L: Integrin Beta-4 boxylmethyltransferase 2: Leucoagglutinating Phytohemag Subunit; Intercellular Adhesion Molecule-1; Intercellular glutinin; Leucoanthocyanidin Dioxygenase; Leucyl-tRNA Adhesion Molecule-2; Interferon gamma receptor including Synthetase; Leucyl-tRNA synthetase, cytoplasmic; Leukoag IFNGR1 and IFNGR2 (IFN-gamma binds directly to glutinin; Leukocidin F Subunit; Leukocyte Elastase; Leuko IFNGR1 and indirectly to IFNGR2); Interferon receptor sialin; Leukotriene A-4 Hydrolase; Leukotriene B4 12-Hy IFNAR1; Interferon receptor IFNAR2c; Interferon Stimu droxydehydrogenase/Pros; Levansucrase; Levodione lated Gene 20 Kda; Interferon-Beta; Interferon-Inducible Reductase: L-Fucose Isomerase: L-Fuculose 1-Phosphate Gtpase: Interleukin 17F: Interleukin-1 type I receptor (IL Aldolase; L-Fuculose-1-Phosphate Aldolase; L-Histidinol 1RI); Interleukin-11 receptor alpha chain (IL-11 R-alpha); Dehydrogenase; light chain; Light chain 1 B72.3 (murine); Interleukin-12 Beta Chain; Interleukin-19: Interleukin-2: Lignin Peroxidase; Limonene-1,2-Epoxide Hydrolase; Interleukin-2 receptor alpha chain (IL-2-RA); Interleukin-2 Lipase; Lipase; Lipase 2: Lipase 3: Lipase, Gastric: Lipid receptor beta chain (IL-2-RB); Interleukin-3 precursor; Inter Transfer Protein; Lipi; Lipoate-Protein Ligase, Putative: mediate conductance Ca(2+)-activated K(+) channel, hIK1; Lipoprotein Mxim; Lipoprotein Nlpi; Lipoxygenase-3; Internalin A: Interphotoreceptor retinoid-binding protein; Lipoyltransferase 1: Lithostathine: Liver Alcohol Dehydro Intestinal Fatty Acid-Binding Protein; Intramolecular Trans genase; Liver Carboxylesterase: Liver Carboxylesterase I; Sialidase; Intron-Associated Endonuclease 1: Invasin; Inver Liver Fatty Acid Binding Protein: Liver Glycogen Phospho tase Inhibitor; Inward rectifier potassium channel 2: Iols Pro rylase; L-Lactate Dehydrogenase; L-Lactate Dehydroge tein; Ionotropic Glutamate Receptor 5; Iota Toxin nase; L-lactate dehydrogenase A chain; L-lactate dehydroge Component Ia, Iota-Carrageenase; Iron; Iron Binding Protein nase A-like 6A: L-lactate dehydrogenase A-like 6B; L-lactate Fbpa; Iron-Utilization Periplasmic Protein; Isoasparty1 dehydrogenase B chain; L-Lactate Dehydrogenase B Chain; Dipeptidase; Isocitrate Dehydrogenase; Isocitrate Dehydro L-lactate dehydrogenase C chain; L-Lactate Dehydrogenase genase; Isocitrate dehydrogenase NAD subunit alpha, mito H Chain; L-Lactate Dehydrogenase M Chain; L-Lactate/ chondrial precursor: Isocitrate dehydrogenase NAD sub Malate Dehydrogenase; Lmaj004.091Aaa; Lmaj004144Aaa unit beta, mitochondrial precursor, Isocitrate dehydrogenase Protein; Long-Chain Fatty Acid Transport Protein; Long NAD Subunit gamma, mitochondrial precursor; Isocitrate chain-fatty-acid-CoA ligase 1: Long-chain-fatty-acid-CoA Dehydrogenase Nadip Cytoplasmic; Isocitrate Lyase; ligase 3; Long-chain-fatty-acid-CoA ligase 4: Long-Chain Isoflavone O-Methylransferase: Isolectin B4: Isoleucine Fatty-Acid-CoaSynthetase; Low density lipoproteins (LDL): tRNA synthetase; Isoleucyl-tRNA Synthetase; Isoliquiritige Low-affinity cationic amino acid transporter-2: Low-Density nin 2'-O-Methyltransferase: Isomerase: Isopenicillin N Syn Lipoprotein Receptor, Lc.2: L-Rhamnose Isomerase; thase; Isopentenyl Diphosphate Delta-Isomerase; L-serine dehydratase; L-Sulfolactate Dehydrogenase; Isopentenyl-Diphosphate Delta-Isomerase: Isovaleryl-Coa L-Threonine-O-3-Phosphate Decarboxylase; L-type amino Dehydrogenase; Ispa/Ispf Bifunctional Enzyme: Iswi Pro acid transporter 1 (LAT1); L-type amino acid transporter 2; tein; Kallikrein; Kallikrein 1: Kallikrein 6: Kanamycin nucle Luciferase; Lumazine Synthase; Luteinizing Hormone otidyltransferase; Kappa-4 Immunoglobulin; Kata Catalase; Releasing Hormone (LHRH) Receptor; L-Xylulose Reduc Kdo-8-Phosphate Synthetase; Kdpg Aldolase; Ketoacyl tase; Lymphocyte function-associated antigen 1 (CD11a anti Reductase; Kex1; Killer Cell Immunoglobulin-Like Recep gen); Lysine Biosynthesis Enzyme: Lysine hydroxylase; tor 2Ds; Kindling Fluorescent Protein; Kinesin; Kinesin Lysozyme: Lysozyme C; Lysozyme Insertion Mutant With US 2008/0220441 A1 Sep. 11, 2008

Ala Inserted; Lysozyme: Lysozyme Mutant With Cys 54 mitochondrial precursor: Mevalonate Kinase; Mgp-40; Mhc Replaced By Thr. Lysyl Oxidase; Lysyl Oxidase; Lysyl Class I Homolog Mic-A; Microcystin-Lr: microsomal trig tRNA synthetase; Lytic Murein Transglycosylase B; lyceride transfer protein; Microtubule Motor Protein Ncd; M=4=Lactate Dehydrogenase; M1 muscarinic acetylcholine Mimochrome IV. Miniaturized Metalloprotei; Mineralocor receptor; M2 muscarinic acetylcholine receptor; Mac-2 Bind ticoid Receptor; Minor Core Protein Lambda 3: Mitchondrial ing Protein; Macromomycin; Macrophage Metalloelastase; carnitine/acylcarnitine carrier protein CACL; Mitochondrial Macrophage Migration Inhibitory Factor; Magnesium-De Aconitase; Mitochondrial Aldehyde Dehydrogenase; Mito pendent Phosphatase-1; Major Allergen I Polypeptide, Fused chondrial aspartate-glutamate carrier protein; Mitochondrial Chain 2.; Major Autolysin; Major Capsid Protein; Major carnitine/acylcarnitine carrier protein; Mitochondrial folate Envelope Protein E: Major Nad; Major Pollen Allergen BetV transporter/carrier; Mitochondrial glutamate carrier 1; Mito 1-L; Major Urinary Protein; Major Urinary Protein 2: Major chondrial glutamate carrier 2: Mitochondrial ornithine trans Urinary Protein I; Malate Dehydrogenase; Malate Dehydro porter 1; Mitochondrial ornithine transporter 2: Mitogen genase; Malate dehydrogenase, cytoplasmic; Malate Dehy Activated Protein Kinase 10; Mitogen-Activated Protein drogenase, Glyoxysomal; Malate dehydrogenase, mitochon Kinase 14; Moad Related Protein; Modification Methylase drial precursor; Malate Synthase G. Male-B363; Malic Hhai; Modification Methylase Rsri; Module-Substituted Chi Enzyme: Malic Enzyme 2: Malonamidase E2: Malonyl Coa: mera Hemoglobin Beta-A; Mol Id: 1; Molecule: 6-Phospho Acyl Carrier Protein Malonyltra; Maltodextrin Glycosyl Beta-Glucosid: Mol Id: 1; Molecule: Adenylate Kinase; transferase; Maltodextrin Phosphorylase; Maltodextrin Chain; Mol Id: 1; Molecule: Bacteriorhodopsin; Mol Id: 1; Binding Protein; Maltodextrin-Binding Protein Male-B133; Molecule: Beta-Lactamase II: Syno; Mol Id: 1; Molecule: Maltogenic Amylase; Maltooligosyl Trehalose Synthase: Carbamate Kinase-Like C; Mol Id: 1; Molecule: Cyto Maltooligosyltrehalose Trehalohydrolase; Maltoporin; Mal chrome C2; Chain: A Mol Id: 1; Molecule: Endo-1,4-Beta tose Binding Protein Fused With Designed; Maltose Trans Xylanase; Mol Id: 1; Molecule: Glutaredoxin; Engineered; port Protein Malk; Maltose-6'-Phosphate Glucosidase; Mal Mol Id: 1; Molecule: Maltodextrin Phosphoryl; Mol Id: 1: tose-Binding Periplasmic Protein; Maltose-Binding Protein; Molecule: Progesterone Receptor, Molecule: Apomyoglo Maltose-Binding Protein Mutant Male31; Maltotetraose bin; Other Details: Cryst; Molecule: Cathepsin B; Ec: 3.4. Forming Amylase; Mandelate Racemase; Manganese Peroxi 22.1; Mutatio; Molecule: Human ADP-Ribosylation Factor dase; Manganese-Dependent Inorganic Pyrophosphatas; 1; S: Molecule: Protein Kinase C Delta Type; Domain; Mannan Endo-1,4-Beta-Mannosidase; Mannanase A. Man Molybdenum Cofactor Biosynthesis Protein; Molybdenum nitol Dehydrogenase; Mannose Receptor; Mannose-6-Phos Cofactor Biosynthesis Protein A: Molybdopterin Biosynthe phate Isomerase; Mannose-Binding Protein A: Mannose sis Cnx1; Molybdopterin Converting Factor Subunit 2: Binding Protein Associated Serin; Mannose-Binding Protein Molybdopterin-Guanine Dinucleotide Biosynthe: Momor C; Mannose-Binding Protein-A; Mannose-Binding Protein din; Mono-ADP-Ribosyltransferase C3; Monoamine oxidase C; Mannosyl-Oligosaccharide 1.2-Alpha-Mannosida; Man A (MAO-A); Monoamine oxidase B (MAO-B); Monocar nosyl-Oligosaccharide Alpha-1,2-Mannosida; Map Kinase boxylate transporter 1; Monocarboxylate transporter 2: P38; Map Kinase-Activated Protein Kinase 2: Maspin Pre Monocarboxylate transporter 3: Monocarboxylate trans cursor, Mast/stem cell growth factor receptor precursor, porter 4: Monocarboxylate transporter 5; Monocarboxylate Matrix Gla-protein; Matrix metalloprotease 2 (MMP-2); transporter 6: Monocarboxylate transporter 7: Monocarboxy matrix metalloprotease 9 (MMP-9); Matrix Metalloprotein late transporter 8: Monocyte Chemotactic Protein 2: Mono ase 3: Matrix Metalloproteinase-16; Matrix Metalloprotein cyte Differentiation Antigen Cd14; Mono-Heme C-Type ase-2: Matrix Metalloproteinase-8; Matrix Porin; Matrix Cytochrome Scya; Monomer Hemoglobin Component III; Porin Outer Membrane Protein F; Matrix protein M2: Mdc Monomer Hemoglobin Component IV: Monomeric Sar Sign1B Type I Isoform; Mdc-Sign2 Type I Isoform; Medium cosine Oxidase; Monomethylamine Methyltransferase Chain Acyl-Coa Dehydrogenase; Melatonin Receptor; Mela Mtmb1; Morphinone Reductase: Motuporin; M-Phase tonin receptor type 1B: Membrane Copper Amine Oxidase; Inducer Phosphatase 2: Mre 11 Nuclease; Mrna Capping Menb: Merozoite Surface Protein-1; Meso-Diaminopimelate Enzyme; Mrna Decapping Enzyme; Mrsd Protein; Mta/Sah D-Dehydrogenase; Metabotropic glutamate receptor 1; Nucleosidase; Mu Class Glutathione S-Transferase Of Metabotropic Glutamate Receptor Subtype 1; Meta-Cleav Isoenz; Mu Class Tetradeca-; Mu-Conotoxin Piiia; age Product Hydrolase; Metallo Beta-Lactamase II; Metal Mu-Conotoxin Smilia; Mucosal Addressin Cell Adhesion lochaperone Atx1; Methionine adenosyltransferase: Molecule-1; Mu-crystallin homolog; Multidrug Resistance Methionine Aminopeptidase; Methionine Aminopeptidase 2: Abc Transporter ATP-Bin: Multidrug Resistance Protein; Methionine Gamma-Lyase; Methionine Synthase; Methion Multidrug Resistance Protein Mexa; Multidrug-Efflux Trans ine synthase reductase; Methionine-R-sulfoxide reductase: porter 1 Regulator Bmr; Multiple Antibiotic Resistance Pro Methionine-R-sulfoxide reductase B2: Methionyl Ami tein Marr; Multiple T-cell antigens (CD1, CD2, CD3, CD5, nopeptidase; Methionyl-tRNA synthetase; Methoxy Mycolic CD5, CD7. CD8); multivitamin transporter; Muscarinic ace Acid Synthase 2: Methuselah Ectodomain; Methyl-Accept tylcholine receptor M3; Muscarinic acetylcholine receptor ing Chemotaxis Protein; Methylaspartate Mutase S Chain; M4; Muscarinic acetylcholine receptor M5; Mutator Mutt Methylated-DNA-protein-cysteine methyltransferase: Meth Protein; Muth; Mycolic Acid Synthase: Myoglobin: Myohe ylcrotonoyl-CoA: Methylcrotonoyl-CoA 2; Methylene Tet merythrin: Myo-Inositol Hexaphosphate Phosphohydrol; rahydromethanopterin Dehydrogen; Methylenetetrahydro Myo-Inositol Hexaphosphate Phosphohydrolase; Myo folate Dehydrogenase/Cy; Methylenetetrahydrofolate Inositol Monophosphatase: Myo-Inositol-1-Phosphate Syn reductase; Methylglyoxal Synthase; Methylmalonate-semi thase: Myo-Inositol-1-Phosphate Synthase; Myo-Inositol-1- aldehyde dehydrogenase; Methylmalonic aciduria protein; Phosphate Synthase-Related Pr; Myosin: Myosin Ie Heavy Methylmalonyl Coa Decarboxylase; Methylmalonyl-Coa Chain; Myosin II Heavy Chain; Myosin II Heavy Chain Carboxyltransferase 12S Su: Methylmalonyl-CoA mutase, Fused To Alpha-Actini; Myosin-3 Isoform; Myristoyl-Coa: US 2008/0220441 A1 Sep. 11, 2008 52

Protein N-Myristoyltransferas; Myrosinase; N Utilization 5a; NADH-ubiquinone oxidoreductase subunit B14.5b: Substance Protein B Homolog: N,N-Dimethylglycine Oxi NADH-ubiquinone oxidoreductase subunit B14.7; NADH dase; N-4 Cytosine-Specific Methyltransferase Pvu; N5-Car ubiquinone oxidoreductase subunit B17.2: Nadp: Nadp boxyaminoimidazole Ribonucleotide Synt; Na/K+/2Cl- co Dependent Non Phosphorylating Glycerald; Nadp-Depen transporter, N-Acetylgalactosamine-4-Sulfatase; dent Alcohol Dehydrogenase; NADP-dependent malic N-Acetylglucosamine-1-Phosphate Uridyltransf: N-Acetyl enzyme; NADP-dependent malic enzyme, mitochondrial glucosamine-6-Phosphate Deacetylase; N-Acetyllac precursor; Nadp-Dependent Mannitol Dehydrogenase; tosaminide Alpha-1,3-Galactosylt; N-Acetylactosaminide Nadp-Dependent Nonphosphorylating Glyceralde; Nadph Alpha-1,3-Galactosyltr; N-Acetyl-L-Ornithine Carbamoyl Dehydrogenase 1: Nadph Dependent Thioredoxin Reduc transferase; N-Acetylneuraminate Lyase; N-Acetylneurami tase; Nadph\: Ferredoxin Oxidoreductase; Nadph-Cyto nate Lyase Subunit; N-Acylamino Acid Racemase: N-acyl chrome P450 Reductase; Nadph-Flavin Oxidoreductase: glucosamine 2-epimerase; Nad; NAD(P) transhydrogenase, Nadp-Malate Dehydrogenase; Nagd Protein, Putative; Nalp: mitochondrial precursor; Nad-Dependent Alcohol Dehydro Namn Adenylyltransferase: Nbla; N-Carbamyl-D-Amino genase; Nad-Dependent Deacetylase 2; Nad-Dependent For Acid Amidohydrolase; Ndx1; Nei Endonuclease Viii-Like 1: mate Dehydrogenase; Nad-Dependent Malic Enzyme: Nad Neocarzinostatin; Neopullulanase; Neopullulanase 2: Dependent Malic Enzyme: Nad-Dependent Malic Enzyme, Neprilysin; N-Ethylmaleimide Sensitive Fusion Protein; Mitochondria; NAD-dependent malic enzyme, mitochon Neural Globin: Neural Hemoglobin; Neural Kinase, drial precursor; Nadh Oxidase; Nadh Oxidase/Nitrite Reduc Nuk=Eph/Elk/Eck Family Recept; Neuraminidase; tase; Nadh Peroxidase; Nadh Pyrophosphatase; Nadh-Azore Neuraminidase; Neuraminidase N2; Neuraminidase N9; ductase, Fmn-Dependent: NADH-cytochrome b5 reductase: Neuroglobin; Neuronal Calcium Sensor 1: Neuropeptide Y: Nadh-Dependent Butanol Dehydrogenase; NADH Neuropsin; Neurotensin receptor type 2: Neurotoxin Bmk ubiquinone oxidoreductase 13 kDa-A subunit, mitochondrial M4; Neurotoxin Bmk37; Neutral amino acid transporter A: precursor, NADH-ubiquinone oxidoreductase 13 kDa-B sub Neutral amino acid transporter B: Neutral Protease II; Neu unit; NADH-ubiquinone oxidoreductase 15 kDa subunit; trophil Collagenase; Neutrophil elastase; Neutrophil Gelati NADH-ubiquinone oxidoreductase 18 kDa subunit, mito nase; Neutrophil Gelatinase-Associated Lipocalin; Neutro chondrial precursor, NADH-ubiquinone oxidoreductase 19 phil-Activating Protein A; NG.NG-dimethylarginine kDa subunit; NADH-ubiquinone oxidoreductase 20 kDa sub dimethylaminohydrolase 1: NG.NG-dimethylarginine dim unit, mitochondrial precursor, NADH-ubiquinone oxi ethylaminohydrolase 2: Nh; Niacin receptor HM74A: Nickel doreductase 23 kDa subunit, mitochondrial precursor: Responsive Regulator; Nicotinamide Mononucleotide Ade NADH-ubiquinone oxidoreductase 24 kDa subunit, mito nylyl Tra; Nicotinamide Mononucleotide Adenylyl Transfe; chondrial precursor, NADH-ubiquinone oxidoreductase 30 Nicotinamide Mononucleotide Adenylyltransfer; Nicotina kDa subunit, mitochondrial precursor, NADH-ubiquinone mide Mononucleotide Adenylyltransfer; Nicotinamide oxidoreductase 39 kDa subunit, mitochondrial precursor: Nucleotide Transhydrogenase; Nicotinamide Nucleotide NADH-ubiquinone oxidoreductase 42 kDa subunit, mito Transhydrogenase; Nicotinamide Nucleotide Transhydroge chondrial precursor, NADH-ubiquinone oxidoreductase 49 nase, Su; Nicotinamide-Nucleotide Adenylyltransferase: kDa subunit, mitochondrial precursor, NADH-ubiquinone Nicotinate D-ribonucleotide phyrophsopate phosphoribosyl oxidoreductase 51 kDa subunit, mitochondrial precursor: transferase: Nicotinate Mononucleotide: 5,6-Dimethylbenzi; NADH-ubiquinone oxidoreductase 75 kDa subunit, mito Nicotinate N-methyltransferase: Nicotinate Phosphoribosyl chondrial precursor, NADH-ubiquinone oxidoreductase 9 transferase: Nicotinate Phosphoribosyltransferase From Th; kDa subunit, mitochondrial precursor, NADH-ubiquinone Nicotinate-Nucleotide Adenylyltransferase; Nicotinate oxidoreductase AGGG subunit, mitochondrial precursor: Nucleotide-Dimethylbenzimidazole; nicotinic acetylcholine NADH-ubiquinone oxidoreductase ASHI subunit, mitochon (ganglion) receptor, Nicotinic acetylcholine Receptor drial precursor, NADH-ubiquinone oxidoreductase B12 sub alpha2/alpha3; Nima-Related Protein; Nine-Haem Cyto unit; NADH-ubiquinone oxidoreductase B14 subunit; chrome C; Nine-Heme Cytochrome C; Nit-Fragile Histidine NADH-ubiquinone oxidoreductase B15 subunit; NADH Triad Fusion Protein; Nitrate Reductase; Nitric Oxide Reduc ubiquinone oxidoreductase B16.6 subunit; NADH tase; Nitric Oxide Synthase: Nitric oxide synthase IIB: Nitric ubiquinone oxidoreductase B17 subunit; NADH-ubiquinone Oxide Synthase, Inducible; Nitric-Oxide Reductase Cyto oxidoreductase B18 subunit; NADH-ubiquinone oxi chrome P450 55A1: Nitric-Oxide Synthase: Nitric-oxide doreductase B22 subunit; NADH-ubiquinone oxidoreductase synthase brain; Nitric-Oxide Synthase Homolog; Nitric-ox B8 subunit; NADH-ubiquinone oxidoreductase B9 subunit; ide synthase IIC; Nitric-Oxide Synthase, Brain; Nitric-Oxide NADH-ubiquinone oxidoreductase chain 1: NADH Synthase, Endothelial; Nitrite Reductase: Nitrogen Fixation ubiquinone oxidoreductase chain 2: NADH-ubiquinone oxi Regulatory Protein Fixl; Nitrogen Regulation Protein; Nitro doreductase chain 3: NADH-ubiquinone oxidoreductase gen Regulatorylia Protein; Nitrogen Regulatory Protein Pii; chain 4: NADH-ubiquinone oxidoreductase chain 4L: Nitrogenase Iron Protein; Nitrogenase Iron Protein 1: Nitro NADH-ubiquinone oxidoreductase chain 5; NADH phorin 1: Nitrophorin 2: Nitrophorin 4: Nitroreductase: ubiquinone oxidoreductase chain 6: NADH-ubiquinone oxi Nitroreductase Family Protein; Nitrosocyanin; Nitrous Oxide doreductase KFYI subunit, mitochondrial precursor, NADH Reductase: Nitrous-Oxide Reductase; Nk Receptor; NMDA ubiquinone oxidoreductase MLRQ subunit: NADH receptor; N-Methyl-D-Aspartate Receptor Subunit 1: Nimra; ubiquinone oxidoreductase MLRQ subunit homolog: Nogalonic Acid Methyl Ester Cyclase. Non Catalytic Protein NADH-ubiquinone oxidoreductase MNLL subunit; NADH 1: Nonaheme Cytochrome C. Non-ATP Dependent L-Selec ubiquinone oxidoreductase MWFE subunit: NADH tive Hydantoina; Non-Catalytic Protein 1: Non-heme chlo ubiquinone oxidoreductase PDSW subunit: NADH roperoxidase; Nonspecific Lipid Transfer Protein: Nonspe ubiquinone oxidoreductase SGDH subunit, mitochondrial cific Lipid-Transfer Protein: Nonstructural Polyprotein precursor, NADH-ubiquinone oxidoreductase subunit B14. Pp 1A: Non-Symbiotic Hemoglobin: Not Applicable: US 2008/0220441 A1 Sep. 11, 2008

NPC1L1 (Niemann-Pick C1 Like 1) Protein transporter; ing Protein 2X; Penicillin-binding protein 3: Penicillin-bind Npqtn Specific Sortase B: Nrdi Protein; NRH dehydrogenase ing protein 4 precursor; Penicillin-Binding Protein 5: Peni quinone 2: Nitpase P4: Nuclear Inclusion Protein A; Nuclear cillin-binding protein 5 precursor; Penicillin-binding receptor OB 1: Nuclear Receptor Ror-Alpha; Nucleoside proteins 1A/1B: Penicillin-insensitive Murein Endopepti 2-Deoxyribosyltransferase: Nucleoside Diphosphate Kinase; dase; Penicillopepsin; Pentaerythritol Tetranitrate Reductase: Nucleoside Diphosphate Kinase A. Nucleoside Diphosphate Penton Protein; Pentosyltransferase: Pepp 1: Peptaibol; Pep Kinase II: Nucleoside Diphosphate Kinase, Cytosolic; tide; Peptide Amidase; Peptide Deformylase; Peptide Nucleoside Diphosphate Transferase: Nucleoside-Specific Deformylase 2: Peptide Deformylase Defb; Peptide Channel-Forming Protein; Nudix Homolog: O6-Alkylgua Deformylase Pdfl; Peptide Methionine Sulfoxide Reductase: nine-DNA Alkyltransferase: Obelin; Odorant Binding Pro Peptide N-Myristoyltransferase: Peptide Transporter Tap 1: tein; Odorant Binding Protein Lush; Odorant-Binding Pro Peptide-N: Peptidic Toxin Nodularin: Peptidoglycan Recog tein; Old Yellow Enzyme: Olfactory Marker Protein: nition Protein I-Alph: Peptidoglycan Recognition Protein Sa Oligopeptide Abc Transporter, Periplasmi; Omegac-Txix: Cg 11709; Peptidoglycan synthetase fisl. Peptidyl-Glycine Omp Synthase: Ompk36; Opioid delta Receptor (OP1); Alpha-Amidating Monooxygena; Peptidylglycine Alpha Opioid kappa Receptor (OP2); Opioid mu Receptor (OP3); Hydroxylating Monooxyg: Peptidyl-Lys Metalloendopepti Opioid sigma 1 Receptor; Opioid sigma Receptor (OP4); dase; Peptidyl-Prolyl Cis-Trans Isomerase; Peptidyl-Prolyl Orange Carotenoid Protein; Orc2: Orexin-A.; Orf, Conserved Cis-Trans Isomerase 5: Peptidyl-Prolyl Cis-Trans Isomerase Hypothetical Protein; Orf3; Organic acid transporter 3 A: Pepv: Peridinin-Chlorophyll Protein: Peripheral nerve (OAT3); organic anion transporter (MRP1, MRP2 and Sodium channel 3: Peripheral nerve sodium channel 5; MRP3, MRP4 and MRP5); Organic cation/carnitine trans Peripheral Plasma Membrane Cask: Periplasmic Divalent porter 1; Organic cation/carnitine transporter 2: Organic Cation Tolerance Pr; Periplasmic Divalent Cation Tolerance Hydroperoxide Resistance Protein: Ornithine Aminotrans Protei: Periplasmic Molybdate-Binding Protein: Peroxidase; ferase: Ornithineaminotransferase, mitochondrial; Ornithine Peroxidase C1A: Peroxidase N; Peroxidase/Catalase T: Per Carbamoyltransferase: Ornithine carbamoyltransferase, oxiredoxin; Peroxiredoxin 5 Residues 54-214; Peroxiredoxin mitochondrial; Ornithine Cyclodeaminase; Ornithine Decar 5, mitochondrial precursor; Peroxisomal bifunctional boxylase: Ornithine decarboxylase antizyme: Ornithine enzyme; Peroxisomal Carnitine O-Octanoyltransfer; Peroxi Transcarbamoylase; Orotidine 5'-Monophosphate Decar somal Carnitine O-Octanoyltransferase; Peroxisomal boxylase: Orotidine 5'-Phosphate Decarboxylase; Orotidine Hydratase-Dehydrogenase-Epim; Peroxisomal Hydratase Monophosphate Decarboxylase; Orphan Nuclear Receptor Dehydrogenase-Epimeras; Peroxisomal multifunctional PXr: Osmolarity Sensor Protein; Osmoprotection Protein; enzyme type 2: Peroxisomal Trans 2-Enoyl Coa Reductase: Osmotically Inducible Protein C; Osteocalcin; O-Succinyl Peroxisome Proliferator Activated Receptor A: Peroxisome benzoate Synthase: Outer Membrane Lipoprotein Lolb: Proliferator Activated Receptor D: Peroxisome Proliferator Outer Membrane Phospholipase A: Outer Membrane Protein Activated Receptor G; pH 2.5 Acid Phosphatase; Phage T4 A: Outer Membrane Protein F: Outer Membrane Protein Lysozyme Insertion Mutant With Ser: Phaseolin; Phenazine Nspa: Outer Membrane Protein Tolc; Outer Membrane Pro Biosynthesis Protein Phzd; Phenazine Biosynthesis Protein tein X: Outer Protein Yopm: Ovalbumin; Ovocleidin; Ovo Phzf: Phenazine Biosynthesis Protein Phzg; Phenol 2-Hy mucoid: Ovotransferrin; Ovotransferrin; Oxygen-Insensitive droxylase Component B: Phenol 2-Monooxygenase; Phenol Nad: Oxygen-insensitive NAD(P)H nitroreductase; Oxygen Hydroxylase; Phenylacetone Monooxygenase; Phenylala Insensitive Nadph Nitroreductase; Oxysterols Receptor LXr nine Ammonia-Lyase; Phenylalanine Ammonia-Lyase 1: Beta: Oxytocin receptor (Neurophysin 1); P protein In Phenylalanine Hydroxylase; Phenylalanine-4-Hydroxylase; cludes: DNA-directed DNA polymerase: P protein Includes: Phenylalanine-Regulated 3-Deoxy-D-Arabino-H; Phenyla DNA-directed DNA polymerase, RNA-directed DNA poly lanyl-tRNA synthetase; Phenylalanyl-tRNA synthetase alpha merase, Ribonuclease H; P/neurokinin 1 Receptor; P1 chain; Phenylalanyl-tRNA synthetase beta chain; Phenyle Nuclease; P2 Myelin Protein; P2 Protein; P2Y12 platelet thanolamine N-Methyltransferase; Phenylethylamine Oxi ADP Receptor; P-30 Protein; P300/Cbp Associating Factor; dase; Pheromone Binding Protein; Pheromone-Binding Pro P35; P450 Epoxidase; P450 Monooxygenase; P450Cin: tein; Pheromone-Binding Protein Asp1; Phoq Histidine P64K; P97; Palmitoyl Protein Thioesterase 1: Palmitoyl-Pro Kinase; Phosphatase; Phosphatase; Phosphate Acetyltrans tein Thioesterase 2 Precursor P-Aminobenzoate Synthase ferase; Phosphate-Binding Protein: Phosphatidylcholine Component I: pancreatic alpha amylase; Pancreatic alpha Transfer Protein: Phosphatidylethanolamine Binding Pro amylase precursor, Pancreatic Hormone; Pancreatic Lipase tein: Phosphatidylethanolamine-Binding Protein: Phosphati Related Protein 1: Pancreatic Lipase Related Protein 2; pan dylinositol 3-Kinase Catalytic Subu: Phosphatidylinositol creatic triacylglycerol lipase; Pancreatic triacylglycerol Phosphate Phosphatase; Phosphatidylinositol Transfer Pro lipase Precursor; Pancreatic Trypsin Inhibitor; Pantoate tein Al; Phosphatidylinositol Transfer Protein Alpha; Phos Beta-Alanine Ligase; Pantoate-Beta-Alanine Ligase; Pan phatidylinositol Transfer Protein Sec14P: Phosphatidylinosi tothenate kinase; Pantothenate Synthetase; Papain; Para-ami tol-Specific Phospholipase: Phosphatidylserine nobenzoate synthase component I; Para-aminobenzoic acid decarboxylase proenzyme; Phosphatidylserine receptor; (PABA); Parathion Hydrolase; Parm; Parvalbumin; Parvalbu Phospho-2-Dehydro-3-Deoxyheptonate Aldolase; Phospho min Alpha; Pbcv-1 DNA Ligase; Pcza361.16; P-D-Man 2-Dehydro-3-Deoxyheptonate Aldolase.: Phosphocarrier nopyranosyl Ester), GDP-Mannose 6-Dehydrogenase; Pea Protein Hpr: Phosphodiesterase 4D: Phosphoenolpyruvate Lectin: Peanut Lectin: Peanut Peroxidase, Major Cationic Carboxykinase; Phosphoenolpyruvate Carboxykinase, Isozym; Pectate Lyase; Pectin Methylesterase; Penicillin V Cytos; Phosphoenolpyruvate Carboxykinase, Cytosolic; Acylase; Penicillin-binding protein 1A: Penicillin-binding Phosphoenolpyruvate Carboxylase; Phosphoenolpyruvate protein 1B: Penicillin-binding protein 2: Penicillin-Binding Mutase; Phosphoenolpyruvate Phosphomutase; Phosphoen Protein 2A; Penicillin-binding protein 2B: Penicillin-Bind Zyme Intermediate Of Fru-2,6-Bi; Phosphofructokinase; US 2008/0220441 A1 Sep. 11, 2008 54

Phosphoglucose Isomerase; Phosphoglycerate kinase; Phos Ppc Decarboxylase Atha13A; Ppca; Ppr; Pr3: Precorrin-6Y phoglycerate kinase 1: Phosphoglycerate kinase, glycoso Methyltransferase/Putative; Precorrin-8X Methylmutase: mal; Phosphoglycerate Mutase; Phosphoglycerate Mutase 1: Precursor Form Of Glucose-Fructose Oxidoredu: Precursor Phosphoglycolate Phosphatase; Phosphoheptose Isomerase: OfPeriplasmic Sugar Receptor; Predicted Amidotransferase: Phosphoinositide-Specific Phospholipase C, I; Phospholi Predicted Cobalamin Binding Protein; Preprotein Translo pase A=2=; Phospholipase A2; Phospholipase A2 Homolog: case Seca; Preprotein Translocase Seca 1 Subunit; Preprotein Phospholipase A2 Homolog 2: Phospholipase A2 inhibitory Translocase Seca Subunit; Prfa; Prion Protein; Probable protein; Phospholipase A2 Isoform 2: Phospholipase A2 Iso 2-Phosphosulfolactate Phosphata; Probable Ammonium form 3: Phospholipase A2, Major Isoenzyme: Phospholipase Transporter; Probable arabinosyltransferase A: Probable ara C; Phospholipase C Delta-1: Phosphomannomutase; Phos binosyltransferase B; Probable arabinosyltransferase C: phomethylpyrimidine Kinase; Phosphonoacetaldehyde Probable Aromatic Acid Decarboxylase; Probable ATP-De Hydrolase; Phosphonoacetate Hydrolase; Phosphopanteth pendent RNA Helicase P47: Probable Butyrate Kinase 2: eine Adenylyltransferase: Phosphoribosyl Anthranilate Probable Cell Division Inhibitor Mind: Probable Cysteine Isomerase: Phosphoribosyl Pyrophosphate Synthetase; Phos Desulfurase: Probable Fosfomycin Resistance Protein; Prob phoribosylamidoimidazole-Succinocar, Phosphoribosy able Glutaminase Ybas; Probable Glutaminase Ybg; Prob lamine-Glycine Ligase; Phosphoribosylformylglycina able Gitpase Engc: Probable GTP-Binding Protein Enga: midine Synth; Phosphoribosylglycinamide Probable Inorganic Polyphosphate/ATP-Nad Kin: Probable Formyltransferase; Phosphoribosyltransferase-Related Pro Inorganic Polyphosphate/ATP-Nad Kin; Probable leucyl tein: Phosphorylated Map Kinase P38-Gamma; Phospho tRNA synthetase, mitochondrial; Probable low molecular serine Aminotransferase; Phosphoserine Phosphatase; Phos weight protein-tyrosine-phosphatase epsP: Probable Malate photriesterase: Phosphotriesterase Homology Protein; Synthase G. Probable Methylisocitrate Lyase; Probable Photoactive Yellow Protein: Photolyase; Phy3 Protein: P-Hy Polysaccharide Deacetylase Pdaa; Probable Pyridoxamine droxybenzoate Hydroxylase; P-Hydroxybenzoate Hydroxy 5'-Phosphate Oxidase; Probable S-Adenosylmethionine: lase Complexed With; P-Hydroxybenzoate Hydroxylase 2-Demethylmen; Probable Serine/Threonine-Protein Kinase; Mutant With Ty; Phytase; Phytochrome Response Regulator Probable Serine/Threonine-Protein Kinase Pel; Probable Rcpa; Phytochrome Response Regulator Rcpb; Phytohemag Serine/Threonine-Protein Kinase Pkn; Probable tautomerase glutinin-L; Pi Glutathione Transferase: Pigment Epithelium ydcE: Probable tyrosyl-tRNA synthetase, mitochondrial; Derived Factor; Pituitary Adenylate Cyclase Activating Po: Probable Uracil Phosphoribosyltransferase: Procarboxypep Placenta Growth Factor; Plasma retinol-binding protein; tidase B: Proclavaminate Amidino Hydrolase; Profilin II: Plasmepsin 2; Plasmepsin II: Plasminogen; Plasminogen Progesterone Receptor; Progesterone Receptor (PR); Pro Activator; Plasminogen Activator Inhibitor-1: Plasminogen gramed Cell Death Protein 8: Programmed Cell Death Pro precursor; Plasmodium proton pump; Platelet Glycoprotein tein 8: Prolactin receptor precursor; Proline Dehydrogenase; Ib Alpha Chain Precurs; Platelet-Activating Factor Acetylhy Proline Iminopeptidase; Proline oxidase; Proline-tRNA Syn drolas; Platelet-Activating Factor Acetylhydrolase; PML thetase; Prolyl Endopeptidase; Prolyl hydroxylase; Prolyl RAR Alpha Protein; Pms 1 Protein Homolog 2: Pnp Oxidase; Oligopeptidase; Prophospholipase A=2=; Propionyl-CoA Pokeweed Antiviral Protein; Pol Polyprotein; Pollen Allergen carboxylase alpha chain; Propionyl-CoA carboxylase beta Phl P1: Poly; Poly ADP-Ribose Polymerase-1; Polyamine chain; Propionyl-Coa Carboxylase Complex B Subunit; Oxidase; Polyandrocarpa Lectin; Polygalacturonase; Polyga Prostacyclin synthase; Prostaglandin D2 receptor; Prostag lacturonase I; Polygalacturonase II; Polygalacturonase Inhib landin E2 receptor, EP1 subtype: Prostaglandin E2 receptor, iting Protein; Polynucleotide Kinase; Polyomavirus Coat EP2 subtype: Prostaglandin Endoperoxide H Synthase-1; Protein Vp1; Polyomavirus Vp1 Pentamer; Polypeptide Prostaglandin F Synthase; Prostaglandin F2-alpha receptor; Deformylase; Polypeptide N-Acetylgalactosaminyltrans Prostaglandin G/HSynthase 1 Precursor: Prostaglandin G/H feras; Polyprotein; Polysialic Acid Capsule Biosynthesis Pro Synthase 2: Prostaglandin H2 Synthase: Prostaglandin H2 tein; Porcine Alpha-Amylase; Porcine Pancreatic Spas Synthase-1; Prostaglandin H2 Synthase-2: Prostaglandin molytic Polypepti; Porin; Porphobilinogen Deaminase; Receptor; Prostaglandin-E2 9-Reductase; Prostate-specific Porphobilinogen Synthase; Possible 3-Mercaptopyruvate membrane antigen (7E11-C5.3 antigen/FOLH1-human/ Sulfurtransf: Possible G-T Mismatches Repair Enzyme: glutamate carboxypeptidase II); Prostatic Acid Phosphatase; Postsynaptic Density Protein; Postsynaptic Density Protein Protease; Protease II; Protease Retropepsin; Protease Syn 95; Potassium Channel; Potassium Channel Blocking Toxin thase and Sporulation Negati; Protease Vii; Protegrin 3: Pro 1; Potassium Channel Protein Rck4; Potassium channel sub tein: Ketosteroid Isomerase: Protein 1D10; Protein Arginine family K member 1: Potassium channel subfamily K member Methyltransferase Prmt3; Protein Arginine N-Methyltrans 2: Potassium channel subfamily K member 6: Potassium ferase 1: Protein C: Protein Fkbi; Protein Kinase C. Protein large conductance calcium-activated channel. Subfamily M. Kinase C Interacting Protein; Protein Kinase C, Theta Type: alpha member 1: Potassium transporter (bacterial); Potas Protein Kinase Ck2; Protein Maf: Protein Methyltransferase sium Voltage-gated channel Subfamily A member 1; Potas Hemk: Protein Ninb: Protein Rdmb: Protein With Similarity sium Voltage-gated channel Subfamily E member 1; Potas To Flavin-Contai; Protein Ybgc: Protein Ybhb: Protein Ycei: sium Voltage-gated channel Subfamily H member 2; Protein Yebr; Protein Yesu: Protein Yfbg: Protein Yof Pro Potassium voltage-gated channel subfamily H member 6: tein Ytnj; Protein: Igfbp-1Antagonist; Proteinase; Proteinase Potassium voltage-gated channel subfamily H member 7; K; Protein-Glutamine Gamma-Glutamyltransferase: Protein Potassium voltage-gated channel subfamily KQT member 1: Glutamine Glutamyltransferase E.; Protein-glutamine Potassium/Sodium Hyperpolarization-Activ; Potassium/So glutamyltransferase E precursor: Protein-Glutamine dium Hyperpolarization-Activated; Potassium-Transporting Glutamyltransferase E3; Protein-L-Isoaspartate; Protein-L- Atpase B Chain; Potassium-transporting ATPase beta chain; Isoaspartate O-Methyltransferase: Protein-Tyrosine Phos Pp60V-Src Tyrosine Kinase Transforming Prot; PPAR-alpha; phatase 1B: Protein-Tyrosine Phosphatase Yoph: Protein-Ty US 2008/0220441 A1 Sep. 11, 2008 rosine Phosphatase, Non-Recept; Protein-Tyrosine ferase; Quinolinic Acid Phosphoribosyltransferase; Quinone Phosphatase, Non-Receptor T. Protein-Tyrosine-Phos Oxidoreductase; Quinone Reductase; Quinone Reductase phatase; Prothrombin; Prothrombin; Prothrombin Fragment Type 2: Quinone-Reductase; Quinoprotein Ethanol Dehydro 1; Protoheme Ferrolyase; Proton-coupled amino acid trans genase; Rab GDP Disossociation Inhibitor Alpha; Rab6 porter 1: Proto-Oncogene Serine/Threonine-Protein; Proto Gtpase; RAC serine/threonine-protein kinase; Rac-Alpha Oncogene Serine/Threonine-Protein Kina; Proto-Oncogene Serine/Threonine Kinase; Radixin: RAF proto-oncogene Tyrosine-Protein Kinase Abl1; Proto-Oncogene Tyrosine serine/threonine-protein kinase; Ramoplanin; Ran; Rap2A; Protein Kinase Lck; Proto-Oncogene Tyrosine-Protein Ras-Related C3 Botulinum Toxin Substrate 1 I; Ras-Related Kinase S. Proto-Oncogene Tyrosine-Protein Kinase Src.: Pro Protein Rab-1 1A: Ras-Related Protein Rab-5A; Ras-Related tooncoprotein; Protoporphyrinogen Oxidase, Mitochondria; Protein Rab-7: Ras-Related Protein Rab-9A, Ras-Related P-Selectin; PseudoaZurin; Pseudocatalase; Pseudomonas Protein Ral-A: Ras-Related Protein Sec4; Rat ADP-Ribosy Aeruginosa Lectin II: Psychrophilic Phosphatase I; Pteridine lation Factor-1; Rat Synapsin I: Re-Rnase6 Ribonuclease: Reductase; Pteridine Reductase 1; Pteridine Reductase 2; Pts Reca; Reca Protein; Receptor Protein-Tyrosine Kinase System, Chitobiose-Specific lib Comp; Pulmonary Surfac Erbb-3 Receptor-Type Adenylate Cyclase Gresag 4.1; tant-Associated Protein A: Pulmonary Surfactant-Associated Recombinant Lignin Peroxidase H8; Recombination Protein Protein D; Pumilio 1: Pur Operon Repressor; Pure: Purine Recr; Red Fluorescent Protein Fp611; Redox-Sensing Tran Nucleoside Phosphorylase; Purine Regulatory Protein Yabi: scriptional Repressor; Regulatory Protein Blar1; Regulatory Purine Trans Deoxyribosylase; Purine-Nucleoside Phospho Protein Teni; Renal Dipeptidase; Renin; Renin; Replicase, rylase; Purple Acid Phosphatase; Purple Acid Phosphatase: Hydrolase Domain; Replication Protein; Resistin; Response Putative Acyl-Coa Thioester Hydrolase Hi0827; Putative regulator pleD; Restriction Endonuclease Bglii; Reticulon 4 Alkylsulfatase Atsk; Putative Alpha-L-Fucosidase; Putative Receptor; Reticulon 4 Receptor; Retinal dehydrogenase 1: Aspartate Aminotransferase; Putative ATP-Dependent Clp Retinal dehydrogenase 2: Retinal Dehydrogenase Type II; Protease Proteoly; Putative Betaine Aldehyde Dehydroge Retinoic acid induced 3 protein; Retinoic acid receptor alpha; nase; Putative Blue Light Receptor; Putative Cellulase; Puta Retinoic Acid Receptor Beta: Retinoic Acid Receptor tive Cellulase Celé: Putative Clc Family, Chlorine Transport Gamma-1: Retinoic Acid Receptor Gamma-2: Retinoic acid Prot: Putative Cytochrome P450; Putative Cytochrome P450 receptor responder protein 1: Retinoic acid receptor RXR 154A1: Putative Family 31 Glucosidase Yici; Putative Flavin alpha; Retinoic acid receptor RXR-beta; Retinoic acid recep Oxidoreducatase; Putative Glur0 Ligand Binding Core: Puta tor RXR-gamma; Retinoid X Receptor, Beta: Retinol Bind tive Glur0 Ligand Binding Core: Putative G-protein coupled ing Protein Complexed With Axero: Retinol Dehydratase: receptor 40; Putative Ketoacyl Reductase; Putative Lipase retinol dehydrogenase 12; retinoldehydrogenase 13; Retinol From The G-D-S-L Family: Putative Mannosyl-3-Phospho binding protein I: Retinol-binding protein II: Retinol-binding glycerate Phospha; Putative Modulator Of DNA Gyrase: protein III: Retinol-binding protein IV: Retropepsin; Reverse Putative Nadph Dependent Oxidoreductases; Putative Gyrase; Rifbc; Rfcs; Rhamnogalacturonan Acetylesterase; Oxalate Decarboxylase; Putative Oxidoreductase RV2002: Rhamnogalacturonase A. Rhamnulose-1-Phosphate Aldo Putative Oxidoreductase RV2002: Putative Phosphatase: lase; Rhizome Secoisolariciresinol Dehydrogenase; Rhoa; Putative Polyprotein/Phosphatase; Putative Protease La Rhodanese; Rhodopsin; Rho-Related GTP-Binding Protein Homolog: Putative Riboflavin Kinase; Putative Snrnp Sm Rhoe: Riboflavin kinase; Riboflavin Kinase/Fmn Adenylyl Like Protein: Putative Sugar Kinase; Putative Transcriptional transferase: Riboflavin Synthase; Riboflavin Synthase Alpha Regulator; Putative Xylanase; Putidaredoxin Reductase: Chain; Ribokinase; Ribonuclease; Ribonuclease 1: Ribonu Putrescine-Binding Protein; Pyelonephritic Adhesin; Pyra clease 4: Ribonuclease A. Ribonuclease Hii; Ribonuclease nose Oxidase; Pyridoxal kinase; Pyridoxal Phosphate Bio Mc; Ribonuclease Mc1; Ribonuclease Pancreatic; Ribonu synthetic Protein Pdx; Pyridoxal phosphate phosphatase: clease pH; Ribonuclease Sa; Ribonuclease T1: Ribonuclease Pyridoxamine Kinase; Pyridoxine 5'-Phosphate Oxidase; U2: Ribonuclease UK114; Ribonuclease Z: Ribonuclease, Pyridoxine 5'-Phosphate Oxidase; Pyridoxine 5'-Phosphate Seminal; Ribonucleoside-Diphosphate Reductase 2 Alpha; Synthase; Pyridoxine-5'-phosphate oxidase; Pyrimidine Ribonucleoside-Diphosphate Reductase M2 Chai; Ribo Nucleoside Phosphorylase; Pyrogenic Exotoxin B: Pyro nucleotide reductase; Ribonucleotide Reductase R2: Ribo phosphatase: Pyrr Bifunctional Protein; Pyrroline-5-car nucleotide Reductase R2-2 Small Subunit; Ribonucleotide boxylate reductase 1: Pyrroline-5-carboxylate reductase 2: Reductase Subunit R2F: Ribose 5-Phosphate Isomerase: Pyrroline-5-carboxylate synthetase; Pyruvate carboxylase; Ribose-5-Phosphate Isomerase A: Ribose-5-Phosphate Pyruvate Decarboxylase; Pyruvate dehydrogenase; Pyruvate Isomerase Rpib: Ribosomal Protein L1; Ribosomal Protein Dehydrogenase E1 Component; Pyruvate dehydrogenase E1 L4: Ribosomal Protein S6 Kinase Alpha 5; Ribosomal Small component alpha Subunit, Somatic form, mitochondrial pre Subunit Pseudouridine Sy; Ribosomal Small Subunit cursor, Pyruvate dehydrogenase E1 component alpha Sub Pseudouridine Syntha; Ribosome Recycling Factor; Ribo unit, testis-specific form, mitochondrial precursor, Pyruvate some-Inactivating Protein Alpha-Trichos: Ribulose-1.5 Bis Dehydrogenase Kinase, Isozyme 2: Pyruvate dehydrogenase phosphate Carboxylase/Oxygen; Ricin; Ricin A Chain; protein X component, mitochondrial precursor, Pyruvate Right-Handed Coiled Coil Tetramer; Right-Handed Coiled Kinase; Pyruvate kinase, isozymes M11/M2; Pyruvate Coil Trimer; RNA 3’-Terminal Phosphate Cyclase; RNA Kinase, Isozymes R/L; Pyruvate Oxidase; Pyruvate Phos Dependent RNA Polymerase: RNA Ligase 2: RNA Poly phate Dikinase; Pyruvate, Orthophosphate Dikinase; Pyru merase Alpha Subunit; RNA-Binding Protein Regulatory vate: ferredoxin oxidoreductase (PFOR) in anaerobes; Pyru Subunit; RNA-Dependent RNA Polymerase: RNA-Directed vate-Ferredoxin Oxidoreductase; Pyruvoyl-Dependent RNA Polymerase: Rnase L Inhibitor; Rnase Ngr3; Rind3/ Arginine Decarboxylase; Pyst1: Quercetin2.3-Dioxygenase; Rhoe Small GTP-Binding Protein; Rod Shape-Determining Queuine tRNA-Ribosyltransferase; Quinohemoprotein Protein Mreb; Rop Ala2Ile2-6; Rubredoxin; Rubredoxin: Alcohol Dehydrogenase; Quinolinate Phosphoribosyl Trans Oxygen Oxidoreductase; Ruvb; Rv3303C-Lpda; Ryanodine US 2008/0220441 A1 Sep. 11, 2008 56 receptor 1: S-Gamma86-Beta-Mercaptoethanol-Lysozyme; SNAP-25; Sniffer Cg10964-Pa; Sodium- and chloride-de S-Gamma97-Beta-Mercaptoethanol Lysozyme: S100A6; pendent creatine transporter 1: Sodium- and chloride-depen S3-Rnase; Saccharopepsin; Saccharopepsin precursor, Sac dent creatine transporter 2: Sodium- and chloride-dependent charopine Reductase; S-Adenosylhomocysteine Hydrolase; GABA transporter 1: Sodium- and chloride-dependent neu S-Adenosyl-L-Homocysteine Hydrolase; S-Adenosyl-L- tral and basic amino acid transporter B(0+); Sodium/Hydro Methionnine: Salicylic Acid Car; S-Adenosylmethionine gen Exchanger 1: Sodium/potassium-transporting ATPase Decarboxylase Proen; S-Adenosylmethionine Decarboxy alpha-1 chain; Sodium/potassium-transporting ATPase lase Proenzyme: S-Adenosylmethionine Synthetase; S-Ad gamma chain; Sodium-dependent norepinephrine re-uptake enosyl-Methyltransferase Mraw; Salicylic Acid-Binding pump; Sodium-dependent proline transporter, Sodium-de Protein 2; Salivary Lipocalin; Salivary Nitrophorin; Salvia pendent serotonin re-uptake pump; Soluble Cytochrome officinalis; Sandostatin: Saposin B: Sarl; Sarcoplasmic/En B562; Soluble Lytic Transglycosylase Slt70; Soluble Quino doplasmic Reticulum Calcium A; Sarcosine Oxidase; Sar protein Glucose Dehydrogenase; Soluble Tumor Necrosis cosine Oxide: Scaffolding Dockerin Binding Protein A; Scav Factor Receptor 1: Solute carrier family 12, member 2: Solute enger receptor class B member 1; Scorpion Neurotoxin; carrier family 12, member 4: Solute carrier family 12, mem Scytalone Dehydratase: SDHA protein; Sec 14-Like Protein ber 5; Solute carrier family 12, member 6: Solute carrier 2: SEC14-like protein 3: SEC14-like protein 4: Sec18P: family 12, member 7: Solute carrier family 13, member 1: Secretin receptor; Sedolisin; Seed Coat Peroxidase; Seed Solute carrier family 13, member 2: Solute carrier family 13, Lipoxygenase-3; Segmentation Polarity Homeobox Protein member 3: Solute carrier family 23 member 1: Solute carrier Engrai; Segregation Protein; Selenocysteine Lyase; Selenos family 23 member 2: Somatostatin receptor type 1: Soma ubtilisin Bpn: Semaphorin 3A. Seminal Plasma Protein Pdc tostatin receptor type 2: Sorbitol Dehydrogenase; Sorting 109; Sensor Kinase Cita; Sensor Protein Fixl; Sensory Nexin Grd 19; splO43272|PROD HUMAN Proline oxidase, Rhodopsin II; Sepiapterin Reductase: Serine Acetyltrans mitochondrial precursor (EC 1.5.3.-) (Proline dehydroge ferase: Serine Carboxypeptidase; Serine Hydroxymethyl nase); sp|P04746|AMYP HUMAN Pancreatic alpha-amy transferase: Serine hydroxymethyltransferase (mitochon lase precursor; sp|P04798|CP1A1 HUMAN Cytochrome drial); Serine Hydroxymethyltransferase, Cytosolic: Serine P450 1A1 (EC 1.14.14.1); sp|P051081C11A HUMAN palmitoyltransferase 1: Serine palmitoyltransferase 2: Serine Cytochrome P450 11A1; sp|P05177|CP12 HUMAN Cyto Protease; Serine racemase; Serine/Threonine Kinase 6: chrome P450 1A2; sp|P05177|CP1A2 HUMAN Cyto Serine/Threonine Protein Kinase Tao2; Serine/Threonine chrome P450 1A2 (EC 1.14.14.1); sp|P05181|CP2E1 HU Protein Phosphatase 5: Serine/Threonine Protein Phos MAN Cytochrome P450 2E1 (EC 1.14.14.1): phatase Pp1-Gam: Serine/threonine-protein kinase sp|P05186|PPBT HUMAN Alkaline phosphatase, tissue ALS2CR7: Serine/threonine-protein kinase receptor R2: nonspecific isozyme precursor; sp|P08263|GSTA 1 HU Serine/threonine-protein kinase receptor R3: Serine/Threo MAN Glutathione S-transferase Al; sp|P08684|CP3A4 HU nine-Protein Kinase Ymir216C; Serine-Carboxyl Proteinase; MAN Cytochrome P450 3A4 (EC 1.14.13.67); Serine-pyruvate aminotransferase: Serotonin N-Acetyltrans sp|P09210|GSTA2 HUMAN Glutathione S-transferase A2; ferase: Serotransferrin; Serotransferrin precursor; Serratia sp|P10632ICP2C8 HUMAN Cytochrome P450 2C8 (EC Marcescens Aminoglycoside-3-N-Acet; Serum Albumin; 1.14.14.1); sp|P10635|CP2D6 HUMAN Cytochrome P450 Serum albumin precursor; Serum Amyloid P Component; 2D6 (EC 1.14.14.1); sp|P11509|CP2A6. HUMAN Cyto Serum Transferrin; Seryl-tRNA synthetase; Set9; Sex Comb chrome P450 2A6 (EC 1.14.14.1); sp|P11712|CP2C9 HU On Midleg Cg.9495-Pa; Sex Hormone-Binding Globulin; Sex MAN Cytochrome P450 2C9 (EC 1.14.13.80); hormone-binding globulin precursor: Sfl 1-Rinase; Sfua; Sh3 sp|P15104|GLNA HUMAN Glutamine synthetase (EC 6.3. Domain-Binding Glutamic Acid-Rich Protein; Shiga Toxin 1.2) (Glutamate-ammonia ligase) (GS); sp|P15289|ARSA B-Chain; Shiga-Like Toxin I B Subunit; Shiga-Like Toxin I HUMAN Arylsulfatase A precursor (EC 3.1.6.8) (ASA) Subunit B: Shiga-Like Toxin lie B Subunit; Shikimate 5'-De (Cerebroside-sulfatase) Contains: Arylsulfatase A compo hydrogenase; Shikimate 5-Dehydrogenase; Shikimate 5-De nent B: Arylsulfatase A component C: sp|P15531 INDKA hydrogenase 2: Shikimate Kinase; Short Chain 3-Hydroxya HUMAN Nucleoside diphosphate kinase A (EC 2.7.4.6); cyl-Coa Dehydrogenase; Short chain 3-hydroxyacyl-CoA sp|P16152|DHCA HUMAN Carbonyl reductase NADPH dehydrogenase, mitochondrial precursor; Short Chain Acyl 1; sp|P16435INCPR HUMAN NADPH-cytochrome P450 Coa Dehydrogenase; Short-Chain Dehydrogenase/Reduc reductase; sp|P190991C11B2 HUMAN Cytochrome P450 tase Family M: Shp-2: Siah-1A Protein; Sialic Acid Binding 11B2.: sp|P19971 TYPH HUMAN Thymidine phosphory Ig-Like Lectin 7: Sialidase; Sialidase 2: Sialoadhesin: Sigfl lase; sp|P2071DDC HUMAN Aromatic-L-amino-acid Gfp Fusion Protein; Sigma Factor Sigb Regulation Protein decarboxylase; sp|P20813|CP2B6 HUMAN Cytochrome Rsbq; Signal Peptidase I: Signal Processing Protein; Signal P450 2B6 (EC 1.14.14.1); sp|P21397|AOFA HUMAN Processing Protein; Signal Recognition Particle 9/14 Fusion Amine oxidase flavin-containing; sp|P22309|UD11 HU Prot; Signal Recognition Particle Protein; Signal Sequence MAN UDP-glucuronosyltransferase 1-1 precursor: Recognition Protein Ffh; Signalling Protein Spb; Silent Infor sp|P22310|UD14 HUMAN UDP-glucuronosyltransferase: mation Regulator 2; Simian Immunodeficiency Virus; Simi sp|P23141|EST1 HUMAN Liver carboxylesterase 1 precur lar To Synaptotagmini/P65: Similar To Thymidylate Kinase; sor (EC 3.1.1.1); sp|P27338|AOFB HUMAN Amine oxi Sindbis Virus Capsid Protein; Single Stranded DNA Binding dase B; sp|P27707|DCK HUMAN Deoxycytidine kinase Protein; Siroheme Biosynthesis Protein Met&; Siroheme (EC 2.7.1.74) (dCK); sp|P28332|ADH6 HUMAN Alcohol Synthase; Skeletal Dihydropydrine Receptor. Smad2; Small dehydrogenase 6 (EC 1.1.1.1); sp|P32320|CDD HUMAN Inducible Cytokine A20; Small inducible cytokine A23 pre Cytidine deaminase (EC 3.5.4.5); sp|P33261|CP2CJ HU cursor: Small Inducible Cytokine A5; Small Inducible Cytok MAN Cytochrome P450 2C19 (EC 1.14.13.80); ine B10; Small Nuclear Ribonucleoprotein Homolog: Small sp|P42898 MTHR HUMAN Methylenetetrahydrofolate Tetraheme Cytochrome C; Sm-Like Archaeal Protein 1: reductase; sp|P479891XDH HUMAN Xanthine dehydroge US 2008/0220441 A1 Sep. 11, 2008 57 nase/oxidase; sp|P48775 IT23O HUMAN Tryptophan 2,3- Capsid Protein Of Pbcv-1, Vp54: Thermal Hysteresis Pro dioxygenase (EC 1.13.11.11) (Tryptophan pyrrolase) (Tryp tein; Thermolysin; Thermonuclease; Thermonuclease pre tophanase) (Tryptophan Oxygenase) (Tryptamin 2,3- cursor; Thermosome Alpha Subunit; Thiamin Phosphate dioxygenase) (TRPO); sp|P50135|HNMT HUMAN Synthase; Thiamin Pyrophosphokinase; Thiamine pyrophos Histamine N-methyltransferase: sp|Q06278 ADO HUMAN phokinase; Thiamine transporter 1: Thiamine triphosphatase; Aldehyde oxidase (EC 1.2.3.1); splQ07973|CP24A HU Thiazide-sensitive sodium-chloride cotransporter; Thiazole MAN Cytochrome P450 24A1; sp|Q16696||CP2AD HU Biosynthetic Enzyme: Thioesterase: Thioesterase I: Thiol MAN Cytochrome P450 2A13 (EC 1.14.14.1): Peroxidase; Thiol: Disulfide Interchange Protein; Thiol-Dis sp|Q6GRKO|Q6GRKO HUMAN Cytochrome P450, sub ulfide Oxidoreductase Resa; Thioredoxin; Thioredoxin family IIIA, polypeptide 4; sp|Q9NTN3|S35D1 HUMAN reductase; Thiostrepton; Threonine Synthase: Threonine syn UDP-glucuronic acid; Sperm Whale Metacuomyoglobin thase-like 1: Threonyl-tRNA Synthetase: Threonyl-tRNA Variant H93G: Spermidine Synthase; Spermidine/Pu Synthetase 1: Thrombomodulin; Thrombospondin 1: Throm trescine-Binding Protein; Spermine oxidase; Sphingosine-1- boxane A2 receptor; Thromboxane A2 synthase; Thrombox phosphate lyase 1: Split-Soret Cytochrome C; Spo0A: ane synthase; Thymidine Kinase; Thymidine Kinase, Cyto SpoOB-Associated GTP-Binding Protein; Spore Coat solic: Thymidine Phosphorylase; Thymidylate Kinase; Polysaccharide Biosynthesis Prote: Spp-40; Squalene Epoxi Thymidylate Synthase; Thymidylate Synthase Thyx; Thy dase; Squalene-Hopene Cyclase, Squalene-Hopene Cyclase; roid hormone receptor alpha; Thyroid Hormone Receptor Sr Protein Kinase; S-Ribosylhomocysteinase; Sst 1-Selective Beta-1; Thyroid hormone receptor beta-2; Thyroid peroxi Somatosatin: Sst 1-Selective Somatosatin Analog: Stapho dase; Thyrotropin receptor (Thyroid stimulating hormone pain; Staphylococcal Enterotoxin B: Stat Protein; Stem/Leaf receptor); Thyroxine-binding globulin precursor; Tick-Borne Lectin Db58; Steroid Delta-Isomerase; Steroid Sulphotrans Encephalitis Virus Glycoprotein; Tissue-Type Plasminogen ferase: Sterol 14-alpha demethylase; Sterol Carrier Protein 2: Activator; Toho-1 Beta-Lactamase; Toll-Like Receptor 2: Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylat Toll-like receptor 7 precursor; Toluene-4-Monooxygenase ing; Steryl-Sulfatase: Sticholysin II: Streptavidin. Streptavi System Protein C; Topoisomerase IV subunit A: Topoi din precursor; Streptogramin A Acetyltransferase; Stringent somerase IV Subunit B: Tora Specific Chaperone; Toxin Starvation Protein A; Stromelysin 3: Stromelysin-1; Struc Bmkk4; tr|Q17328|Q17328. CAEEL Avermectin-sensitive tural Polyprotein; Subtilisin 8321; Subtilisin 8324; Subtilisin glutamate-gated chloride channel GlucI beta; Bpn"; Subtilisin BPN' 8350; Subtilisin Carlsberg: Subtilisin tr|Q46759|Q46759 ECOLI Beta-lactamase; Carlsberg, Type Viii; Subtilisin Pb 92; Subtilisin-Carlsberg: tr|Q5VUYOIQ5VUYO HUMAN Novel protein similar to Subunit C. Succinate dehydrogenase; Succinate semialde esterases; tr|Q75NA5|Q75NA5 MUSDO GABA-gated hyde dehydrogenase, mitochondrial precursor, Succinylargi chloride channel subunit; tr|Q8ITG2|Q8ITG2 CAEEL nine Dihydrolase; Succinyl-CoA ligase GDP-forming beta GABA-A receptor subunit; Trafficking Protein Particle Com chain; Sucrose Phosphorylase; Sucrose-Specific Porin: Sugar plex Subunit; Trai Protein; Transaldolase; Transcarboxylase Transport Protein; Sulfatase Modifying Factor 2; Sulfate 5S Subunit; Transcobalamin I; Transcobalamin II; Transcrip Adenylyltransferase; Sulfide Dehydrogenase; Sulfite Oxi tion Antitermination Protein Nusg: Transcription Antitermi dase; Sulfite Reductase; Sulfite Reductase Hemoprotein; Sul nator Lict; Transcription factor PPARgamma; Transcrip folipid Biosynthesis; Sulfolipid Biosynthesis Protein Sqd1; tional Activator Tena; Transcriptional Regulator; sulfonyl urea receptor (SUR1); Sulfonylurea receptor 1; Sul Transcriptional Regulator Nadr, Transcriptional Regulator, fonylurea receptor 2; Sulfotransferase; Sulfotransferase Fam Hth 3 Family: Transcriptional Regulator, Rok Family; Tran ily, Cytosolic, 2B, Memb; Sulfurtransferase: Superoxide Dis scriptional Regulatory Protein Fixi: Transcriptional Regula mutase; Superoxide Dismutase Cu-Zn; Superoxide tory Protein, Sir2 Fam; Transcriptional Repressor Ethr: Dismutase Fe: Superoxide Dismutase Mn). Mitochondrial; Transducin-Alpha; Transferrin Receptor Protein; Transform Superoxide Dismutase Ni: Suppressor Of Tumorigenicity ing Growth Factor-Beta 3: Transforming Protein P21/H-Ras 14: Surface Layer Protein; Surface Protein; Survival Protein 1: Transforming Protein Rhoa; Transhydrogenase Diii; Tran E: Synapsin Ia: Synthetic Designed Peptide Alpha-1: Syn sient Receptor Potential-Related Protein; Transitional thetic Peptide Analogue Of Shk Toxin; System Namino acid Endoplasmic Reticulum Atpas. Transitional Endoplasmic transporter 1; T Lymphocyte Activation Antigen; T3-785: T4 Reticulum Atpase; Transketolase; Transketolase-like 1: Lysozyme; Tachylectin-2, Tagatose-Bisphosphate Aldolase Translation Elongation Factor Selb; Translation Initiation Agay; Tailspike Protein; Taka Amylase; Tandem pH Domain Factor Eif4E: Translation Initiation Factor If2/EifSB; Containing Protein-1; Taq DNA Polymerase: Taste receptor Transpeptidase (bacterial); Transposase Inhibitor Protein type 1 member 1: Taste receptor type 1 member 2: Taste From Tn5; Trans-Sialidase; Transthyretin: Transthyretin pre receptor type 1 member 3: Tatd-Related Deoxyribonuclease: cursor; Transthyretin Thr119Met Variant; Trehalose Operon Tat-Interacting Protein Tip30; T-Cell Ecto-ADP-Ribosyl Repressor; Triacylglycerol Lipase, Gastric; Triacyl-Glyc transferase 2: T-Cell Ecto-ADP-Ribosyltransferase 2; T-cell erol-Hydrolase; Trichodiene Synthase; Trichotoxin A50E: surface glycoprotein CD3 epsilon chain (CD3E); Tap-Glu Tricorn Protease; Trifunctional enzyme alpha subunit, mito cose-4,6-Dehydratase; Tdp-Glucose-4,6-Dehydratase: chondrial precursor; Trigger Factor, Triggering Receptor Techylectin-5A: Tem-1 Beta Lactamase; Tem-1 Beta-Lacta Expressed On Myeloid Cel; Trihydroxynaphthalene Reduc mase; Terminal Deoxynucleotidyltransferase Short I; Teta tase; Trimethylamine Dehydrogenase; Triose Phosphate nus Toxin; Tetanus Toxin He; Tetanus Toxin Heavy Chain; Isomerase; Triosephosphate Isomerase; Triosephosphate Tetra-; Tetracycline Repressor; Tetrahydrodipicolinate Isomerase, Glycosomal; Trk System Potassium Uptake Pro N-Succinyltransferase; Tetrameric Beta-Beta-Alpha Mini tein Trka Hom; tRNA, tRNA Cca-Adding Enzyme; trNA Protein: Tgf-Beta Receptor Type I: Tgf-Beta Receptor Type Nucleotidyltransferase; thNA-Guanine Transglycosylase; II: Th10Aox: Th1 OBox: Th1 Ox; Thaumatin I: The GTP Tropinone Reductase-I; Tropinone Reductase-II; Troponin Binding Protein Obg: The Hypothetical Protein; The Major C. Slow Skeletal and Cardiac Muscles; Troponin I, cardiac US 2008/0220441 A1 Sep. 11, 2008

muscle; Troponin T. cardiac muscle; Trp Operon Repressor; cosylase Inhibitor; Ure2 Protein: Urease alpha subunit; Trp Repressor Binding Protein Wrba; Trp RNA-Binding Uricase; Uridine Diphospho-N-Acetylenolpyruvylglucosa; Attenuation Protein Complexed: Trypanothione Oxidoreduc Uridine Phosphorylase; Uridine Phosphorylase, Putative: tase; Trypanothione Reductase; Tryparedoxin II; Trypsin; Uridine-Cytidine Kinase 2; Uridylate Kinase; Uridylmono Trypsin I; Trypsin II, Anionic; Trypsin Inhibitor Bgit; Trypsin phosphate/Cytidylmonophosphate Kin: Urocanase Protein; Inhibitor I; Trypsin Iva; Trypsinogen; Tryptamine D recep Urocanate Hydratase; Urokinase; Urokinase-Type Plasmino tors (5HT2B); Tryptophan 2,3-dioxygenase; Tryptophan gen Activator, Uroporphyrin-III C-Methyltransferase: 5-hydroxylase 1: Tryptophan 5-hydroxylase 2: Tryptophan Uroporphyrinogen Decarboxylase; Vacuolar ATP Synthase 5-Monooxygenase; Tryptophan Synthase Alpha Chain; Tryp Subunit C; Valyl-tRNA synthetase; Vanadium Bromoperoxi tophan Synthase Alpha Chain, Chloroplast; Tryptophan dase; Vanillyl-Alcohol Oxidase; Variant Surface Glycopro tein; Vascular endothelial growth factor; Vascular endothelial tRNA Ligase: Tryptophanyl-tRNA Synthetase; Tt0826; growth factor receptor 2 precursor; Vascular endothelial Ttk00300 1606; Tubby Protein; Tubulin; Tubulin alpha chain; growth factor receptor 3 precursor; Vascular Endothelial Tubulin alpha-1 chain; Tubulin alpha-2 chain; Tubulin Growth Factor Toxin; Vasopressin V1a receptor; Vasopressin alpha-3 chain; Tubulin alpha-6 chain; Tubulin alpha-8 chain; V1b receptor; Vasopressin V2 receptor; Vasopressin V2 Tubulin alpha-ubiquitous chain; Tubulin beta chain; Tubulin receptor, Neurophysin 2; Venom Serine Proteinase; Venom beta-1 chain; Tubulin beta-2C chain; Tubulin beta-3 chain; Serine Proteinase; Vesicular Monoamine Transporter; Vhh Tubulin beta-4 chain; Tubulin beta-4q chain; Tubulin-Spe R2 Anti-Rró Antibody; Vim-2 Metallo-Beta-Lactamase: cific Chaperone A.; Tumor Necrosis Factor Alpha; Tumor Vimentin; Viral guanylyltransfearse; Viral RNA polymerase: necrosis factor precursor; Type 2 Malate/Lactate Dehydroge nase; Type 2 Rhinovirus 3C Protease; Type 4 Pilin; Type II Virb11 Homolog:Vitamin B12 Receptor; Vitamin B12 Trans DNA Topoisomerase Vi Subunit B: Type II Quinohemopro port Protein Btuf, Vitamin D Binding Protein; Vitamin D tein Alcohol Dehydrogena; Type III Chloramphenicol Receptor; Vitamin D3 Receptor; Vitamin D-Dependent Cal Acetyltransferase; Type III phosphodiesterase; Type III cium-Binding Prote: Vitamin K Reductase; Vitamin K-de Secretion Chaperone Syce; Type T Voltage gated calcium pendent protein Z: Voltage gated sodium channel; Voltage channel; Type-1 angiotensin 11 Receptor (AT1); Tyrosinase dependent L-type calcium channel alpha-1C Subunit; precursor, Tyrosine 3-Monooxygenase; Tyrosine Ami Voltage-dependent L-type calcium channel beta-1 subunit; notransferase: Tyrosine Phenol-Lyase; Tyrosine Phos Voltage-dependent P/O-type calcium channel alpha-1A sub phatase; Tyrosine-protein kinase ABL2: Tyrosine-Protein unit; Voltage-dependent T-type calcium channel; Voltage Kinase Btk; Tyrosine-Protein Kinase Itk/Tsk; Tyrosine-Pro Gated Potassium Channel; Voltage-gated Sodium channel; tein Kinase Receptor Tyro3: Tyrosine-Protein Kinase Syk: Volvatoxin A2: Vp1 Protein; Vp39; Vsv Matrix Protein: Tyrosine-Protein Kinase Zap-70; Tyrosine-protein phos V-Type Sodium ATP Synthase Subunit K: W224HVariant Of phatase, non-receptor type 1: Tyrosyl-tRNA Synthetase: S. Enterica Rimla Bound To U; Wbpp. Wheat Germ. Aggluti Tyrosyl-tRNA synthetase, cytoplasmic; U1A RNA Binding nin; Winged Bean Lectin; Wiskott-Aldrich Syndrome Pro Domain, Ubiquinol-cytochrome-c reductase complex core tein; Wunen-Nonfunctional Gfp Fusion Protein; Xaa-Pro protein I, mitochondrial precursor, Ubiquitin: Ubiquitin-Ac Aminopeptidase; Xaa-Pro Dipeptidase; Xanthan Lyase; Xan tivating Enzyme E1 1, Ubiquitin-Conjugating Enzyme E22; thine Dehydrogenase: Xanthine oxidase; Xanthine Phospho Ubiquitin-Conjugating Enzyme E2-25 Kda; Ubiquitin-Like ribosyltransferase: Xanthine-Guanine Phosphoribosyltrans Protein 7, Rub 1: Ubiquitin-Protein Ligase E3 Mdm2; Udp ferase; Xanthosine Phosphorylase; Xenobiotic 3-O-3-Hydroxymyristoyl N-Acetylglucosa; Udp-Galacto Acetyltransferase: Xylanase; Xylanase 10C; Xylanase pyranose Mutase; Udp-Galactose 4-Epimerase; Udp-Galac Inhibitor Protein I; Xylanase Y; Xyloglucan Endotransglyco tose 4-Epimerase; Udp-Galactose-4-Epimerase; Udpglenac sylase; Xylose Isomerase: Xylose Reductase: Xylose Reduc Pyrophosphorylase; Udp-Glucose 4-Epimerase: Udp-Glu tase; Y177F Variant Of S. Enterica Rimla Bound To U; Yajq cose 4-Epimerase; UDP-glucose 6-dehydrogenase; Udp Protein; Ydrs33C Protein: Yeast Cytochrome C Peroxidase; Glucose Dehydrogenase; UDP-glucuronosyltransferase 1-9 Yeast Iso-1-Ferrocytochrome C; Yeco; Yfua; Yibi Protein; precursor, microsomal; Udp-N-Acetylenolpyruvoylglu Yigf Protein; Ykof: Ylmd Protein Sequence Homologue: cosamine Reductas; Udp-N-Acetylglucosamine 1-Carbox Ylr011 Wp: Ynk-Contryphan: Yvrk Protein: Zervamicin lib; yvinylt: Udp-N-Acetylglucosamine 1-Carboxyvinyl-Trans; Zinc FingerY-Chromosomal Protein; and Zinc-Alpha-2-Gly UDP-N-acetylglucosamine 1-carboxyvinyltransferase: Udp coprotein. N-Acetylglucosamine 2-Epimerase; Udp-N-Acetylglu Complete System for Analysis cosamine Enolpyruvyl Tran; Udp-N-Acetylglucosamine Enolpyruvyl Transfer, Udp-N-Acetylglucosamine Pyrophos I0083. In order to determine binding constants using phorylase; Udp-N-Acetylglucosamine-1-Phosphate X-Ray fluorescence, a system must be created that is capable Uridyltr; Udp-N-Acetylglucosamine-N-Acetylmuramyl-: of measuring the X-Ray fluorescence of the bound small Udp-N-Acetylmuramate-Alanine Ligase; Udp-N-Acetylmu molecule or drug. A process must exist for equilibrating the ramate-L-Alanine Ligase; Udp-N-Acetylmuramoylalanyl chemical with the protein, this process requires the combina D-Glutamate- Udp-N-Acetylmuramoyl-L-Alanine: tion of the chemical and the protein in Solution, and incuba D-Glutam; Udp-N-Acetylmuramoyl-L-Alanine: tion of the chemical and protein solution for sufficient time to D-Glutamate; Udp-N-Acteylglucosamine Pyrophosphory ensure that chemical equilibrium is obtained; separating the las; Ulex Europaeus Lectin II: Ultraspiracle Protein; UMP unbound/excess Small molecule in a manner that does not CMP kinase; Uncoordinated protein 63: Unknown Protein; unacceptably perturb the binding, and assaying the protein for Unknown Protein From 2D-Page: Unlocked Metal-Free Con the bound molecule, which requires that the separation be canavalin A; Unsaturated Glucuronyl Hydrolase; Upf)230 obtained in less than 5 minutes at 37 degrees Celsius, and Protein Tm 1468; Upper Collar Protein: Uracil Phosphoribo more preferably in less than one minute at 4 degrees Celsius, syltransferase; Uracil-DNA Glycosylase; Uracil-DNA Gly and most preferably in less than 30 seconds at 4 degrees US 2008/0220441 A1 Sep. 11, 2008 59

Celsius. In the case of XRF, one or more atoms in the chemi tem be configured so that no two individuals have the same cal fluoresces when irradiated with X-Rays. This x-ray fluo combination of identification code and password. It is also rescence signal can be used to determine the concentration of preferable that the identification code and password issuances the bound small molecule when proper calibration is used. are periodically checked, recalled, or revised (e.g., to cover Calibration is especially important for X-ray fluorescence, Such events as password aging). It is important that the system and is more important for X-ray fluorescence than for optical be configured so that following loss management procedures fluorescence, because the X-ray penetration depths of differ to electronically deauthorize lost, stolen, missing, or other wise potentially compromised tokens, cards, and other ent chemical elements vary greatly. In contrast to optical devices that bear or generate identification code or password fluorescence where the optical clarity of the sample and the information, and to issue temporary or permanent replace sample holder is easy to assess; in X-ray fluorescence, the ments using Suitable, rigorous controls; and that transaction X-ray attenuation in the sample and the effect of secondary safeguards to prevent unauthorized use of passwords and/or excitation from the Substrate and secondary excitation within identification codes, and to detect and report in an immediate the sample can be large and unpredictable. and urgent manner any attempts at their unauthorized use to I0084. The intensity of the XRF fluorescence of the small the system security unit, and, as appropriate, to organizational molecule can be compared in a ratio against the intensity of management are used. atoms in the protein, or the concentration of the bound mol ecule can be compared to known values from the set up of the Method for Using XRF to Monitor Protein Quality binding experiments to calculate binding constants. For example, a protein can be incubated with an inhibitor under a I0086. Many proteins such as insulin, vaccines, antibodies, range of conditions from very low binding to very high bind human growth hormone (hGH), and clotting factor VIII are ing (close to 100% of the protein). The unbound ligand is produced by pharmaceutical companies. These proteins must separated via gel filtration or another size exclusion tech have high purity to be able to be used safely in humans. nique, and an aliquot from each sample is spotted onto a Quality is very difficult and expensive to monitor for proteins. substrate for XRF measurement. From the intensity of the These methods often require days to complete and significant fluorescence, a concentration of bound Small molecule can be labor. Thus, improved method of monitoring quality in pro determined. A preferred method for assessing binding con teins is needed. stants consists of measuring the intensity of the X-ray fluo I0087. The present invention includes a method for the rescence signal that is due to an atom in the bound chemical; simple, inexpensive, and rapid method of determining protein converting the measured intensity into a concentration value, purity. Many proteins have atoms detectable by XRF, and preferably using a computer, plotting the concentration as a properly functional proteins are coordinated by other atoms saturation isotherm; and extracting the binding constant via such as metals that also are detectable by XRF. There are two fitting of this isotherm through non-linear regression. ways these facts may be exploited: First, a known pure sample 0085. The system preferably has security systems for elec may be measured and the elemental composition determined tronic records, electronic signatures, and handwritten signa to establish a baseline for metal ratios in pure samples; this tures executed to electronic records to be trustworthy, reli baseline may be compared with test samples to see if the able, and generally equivalent to paper records and purity and functionality match. Second, the correct Stoichi handwritten signatures executed on paper for any records in ometry between coordinating metals and the proteins may be electronic form that are created, modified, maintained, known, and the composition of the protein may be known, so archived, retrieved, or transmitted. The security system can a ratio between the coordinating metal and the protein may be be conveniently provided by a biometric analysis, i.e. a used to provide a purity and functionality measurement. For method of verifying an individual's identity based on mea example, there are 24 Sulfur atoms for every two Zinc atoms in surement of the individual's physical feature(s) or repeatable functional insulin, there are four sulfur atoms for every two action(s) where those features and/or actions are both unique Zinc atoms in functional hCGH, and there are 23 sulfur atoms to that individual and measurable. The security system may for every one copper atom. be conveniently provided by means of maintaining a closed system, i.e. an environment in which system access is con Method of Determining a Thermodynamic Binding Constant trolled by persons who are responsible for the content of I0088 A thermodynamic binding constant between two electronic records that are on the system. The security system binders may be measured by contacting a known amount of may be conveniently provided by means of digital signatures, each binder, removing unbound material, and measuring the i.e. an electronic signature based upon cryptographic meth amount of bound material using XRF. This is according the ods of originator authentication, computed by using a set of chemical equilibrium equation k=B1B2/B1B2, where rules and a set of parameters such that the identity of the B1 is the concentration of the first binder, B2 is the con signer and the integrity of the data can be verified. It is centration of the second binder, B1B2 is the concentration preferable that digital signatures that do not use biometric of the two binders bound to each other. This can be done more analysis should employ at least two distinct identification easily if the second binder (B2) has a unique, XRF-measur components such as an identification code and password. It is able atom (i.e., one that is larger than oxygen and that is not preferable that the system be configured such that when an contained within the first binder). individual executes a series of signings during a single, con tinuous period of controlled system access, the first signing EXAMPLE shall be executed using all electronic signature components; Subsequent signings shall be executed using at least one elec I0089. An embodiment of the present invention is tronic signature component that is only executable by, and described in the following example. A 1 microliter sample of designed to be used only by, the individual; and when an protein or protein-chemical complex is diluted and re-sus individual executes one or more signings not performed dur pended by adding 10 microliters of a buffer compatible with ing a single, continuous period of controlled system access, protein of interest, and Vortexed using a Thermolyne Maxi each signing shall be executed using all of the electronic Mix PlusTM and centrifuged using a Revolutionary Science signature components. It is especially preferable that the sys Microcentrifuge at between 6,000 RPM and 10,000 RPM. US 2008/0220441 A1 Sep. 11, 2008 60

Matrix modifiers, such as acetic acid and an internal standard Exposure of the receptor(s) to the chemical(s) may, or may are added at this point. Acetic acid is used in amounts to be not result in the formation of one or more complexes that are equivalent to 2% of the total volume of protein sample. If an referred to herein as “chemical-receptor complexes’. If an internal standard is used, the internal standard reagent is analog of the chemical is used, then the corresponding com mixed with acetic acid to obtain an 8% solution of acetic acid plex is referred to herein as an “analog-receptor complex”. If with internal standard. Typically, a 3:1 solution of protein to the chemical is a drug, then the corresponding complex is internal standardinacetic acid is mixed to end up with protein referred to herein as “drug-receptor complex”. Exposure of in 2% acetic acid solution. The Volumes required for increas the receptor to the chemical/analog/drug allows such a com ing amounts of protein to create standard curve are deter plex to form, if it forms at all, under the conditions of tem mined, and the amounts are mixed accordingly. One then perature, elapsed time, presence of other chemicals or recep aliquots desired amounts into 1.5 ml tubes (Eppendorf Safe tors, receptor concentration, chemical concentration, and Lock tubes rated up to 30,000 g) for each individual protein: other parameters. reagent ratio. The aliquots are then Vortexed and centrifuged. 0095. After sufficient time has elapsed for one of the afore A slide is prepared with the desired substrate (i.e. polypropy mentioned complexes to form, the X-ray fluorescence signal lene, ultralene, mylar, kapton, aluminum, gold) by mounting due to the “heavy element (e.g. phosphorus, chlorine, fluo film on a cardboard or plastic slide mount. Using a pipette or rine, Sulfur, to name a few) in each chemical-receptor com Syringe, protein solution is dispensed onto the Substrate. For plex is measured. a larger spot, a pipette (Eppendorf Series 2000 adjustable 0096. After measuring the XRF signal due to the heavy pipettes) is used to dispense 1 microliter of protein Solution element, the baseline X-ray fluorescence signal is subtracted onto film, while the operator is careful not to fully evacuate from this measured X-ray fluorescence signal; the difference the pipette tip. The sample is preferably deposited by stop is referred to herein as the “net X-ray fluorescence signal'. ping at the first stop on pipette and touching the solution bead The net X-ray fluorescence signal is proportional to the on end of tip to film to release the sample without blowing air amount of the chemical that is bound to the receptor in a into sample. For a smaller spot, use a syringe (Hamilton chemical-receptor complex. Each net-X-ray fluorescence sig 7000.5 KHO.5ul 25/2.76"/3 REVT) and draw from 0.1 to 0.5 nal may be standardized by dividing by the amount of the microliters of sample into Syringe. Dispense sample onto film receptor in the portion used for binding to the chemical. The by depressing Syringe completely and then touching film to amount of receptor typically may have units such as mol release bead onto film. The spot is dried under a heat lamp ecules, moles, moles per liter, grams, grams per liter, units of (GE Halogen SP 10° Beam 100W 120V) for 5 minutes. The activity, and the like. If the same amount of receptor is used sample is then measured using X-ray fluorescence on an for each experiment, then each net X-ray fluorescence signal EDAX Eagle III micro X-ray fluorescence system equipped may be directly compared. with a rhodium target excitation source (40 kV. 1000 uA) and 0097. In addition, the net XRF signal should be standard a SiLi detector. Initial Screening measurements are collected ized for the concentration of chemical if receptors are with an excitation beam dwell time of 100 milliseconds. exposed to solutions having different concentrations of the Detailed analyses of individual samples are collected with an chemical. excitation beam dwell time of 100 to 600 seconds. Measure 0098. The standardized XRF signals obtained using this ments will be standardized by normalizing the RPM intensity invention may then be compared in a variety of ways. One in control samples to the RPM signal in the experimental standardized X-ray fluorescence signal may be subtracted sample. from another signal, for example. One standardized XRF 0090 Briefly, the present invention relates to using X-ray signal may be divided by another signal. Preferably, when fluorescence (XRF) as a probe to determine binding selectivi making comparisons among more than two signals, the sig ties of chemicals for receptors. The invention can also be used nals are plotted on a graph so that comparisons among them to estimate therapeutic index of a chemical. Another aspect of may be easily visualized. the invention relates to providing an estimate of the relative 0099. Another aspect of this invention is related to esti therapeutic indices of two chemicals. mating the binding selectivity of at least two chemicals to two 0091 An aspect of this invention is related to estimating or more receptors and comparing their selectivities. For this the binding selectivity of a chemical to two or more receptors. aspect of the invention, each chemical must include at least The receptors are preferably proteins or other biological one heavy element. The two or more chemicals may include ligands. The receptors may be arrayed on a Substrate. Arrays the same heavy element or different heavy elements. The that include from about 2 to about 100,000,000 receptors, receptors, preferably proteins or other biological ligands, preferably from about 2 to about 1,000,000, and more pref may be arrayed on a Substrate. Arrays may include from about erably from about 2 to about 100,000 are especially useful 2 to about 100,000,000 receptors, preferably from about 2 to with this invention. about 1,000,000, and more preferably from about 2 to about 0092 Chemicals used with this invention generally 100,000. A measured or calculated baseline X-ray fluores include at least one element with an atomic number of nine or cence signal would be obtained for the heavy element(s) in higher; these elements are referred to herein as “heavy ele each portion or aliquot of each receptor used with the inven ments. tion. After establishing the baseline X-ray fluorescence sig 0093 Generally, a baseline XRF signal is established for a nal, the receptors are exposed to a plurality of chemicals, heavy element in each portion oraliquot of each receptor used preferably in solution, which are being tested for binding to with the invention. The baseline x-ray fluorescence signal the receptors. Exposure of the receptors to the chemicals may may be calculated or measured. or may not result in the formation of one or more complexes 0094. After establishing the baseline XRF signal, the that are referred to herein as “chemical-receptor complexes’. receptor(s) are exposed to one or more chemicals, preferably Exposure of the receptor to the chemicals allows Such com in Solution, that are being tested for binding to the receptor(s). plexes to form, if they form at all, under the conditions of US 2008/0220441 A1 Sep. 11, 2008

temperature, elapsed time, presence of other chemicals or drug is a mixture of chemicals, then one of the active ingre receptors, receptor concentration, chemical concentration, dients of the drug must have a heavy element. and other parameters. After sufficient time has elapsed for one 0103) An aspect of this invention is related to estimating of the aforementioned complexes to form, the X-ray fluores the binding affinity of a chemical to one or more receptors, cence signal due to the "heavy element (e.g. phosphorus, preferably proteins or other biological ligands that are chlorine, fluorine, Sulfur, to name a few) in each chemical arrayed on a substrate. The chemical would include at least receptor complex is measured. After measuring the X-ray one heavy element. First, a baseline XRF signal for the heavy fluorescence signal due to the heavy element(s), the baseline element in each portion or aliquot of each receptor would be X-ray fluorescence signal is Subtracted from this measured obtained, either by measuring or calculating the baseline sig X-ray fluorescence signal; the difference is referred to herein nal. Afterward, the receptor(s) would be exposed to one or as the “net X-ray fluorescence signal'. The net X-ray fluores more chemicals. Chemicals that bind to the receptors result in cence signal is proportional to the amount of the chemical that the formation of chemical-receptor complexes that are detect is bound to the receptor in a chemical-receptor complex. able by measuring the XRF signal due to the heavy element in each chemical-receptor complex. This measured X-ray fluo Next, each net X-ray fluorescence signal is standardized by rescence signal is obtained by using X-ray excitation photons dividing by the amount of the receptor in the portion used for with an energy of at least 300 eV, which generate emission binding to the chemical. The amount of receptor typically photons having a fluorescence lifetime that is less than the may have units such as molecules, moles, moles per liter, dead time of the X-ray detector. After measuring the X-ray grams, grams per liter, units of activity, and the like. If the fluorescence signal due to the heavy element, the baseline same amount of receptor is used for each experiment, then XRF signal is subtracted from this measured x-ray fluores each net X-ray fluorescence signal may be directly compared. cence signal, yielding the net XRF signal, which is propor The standardized X-ray fluorescence signals may be com tional to the amount of the chemical that is bound to the pared in a variety of ways. One standardized X-ray fluores receptor in a chemical-receptor complex. The net XRF signal cence signal may be subtracted from another signal, for would then be standardized. The standardized XRF signals example. One standardized X-ray fluorescence signal may be may then be compared. divided by another signal. Preferably, when making compari 0104. The invention can also be used to detect modifica Sons among more than two signals, the signals are plotted on tions in proteins. Examples of such detectable protein modi a graph so that comparisons among them may be easily visu fication include, but are not limited to, post-translational alized. modification of proteins, phosphorylation of proteins, and 0100. The invention also relates to drug manufacturing. dephosphorylation of proteins. Detecting these modifications The drug manufacturing process includes the determination would typically begin by first establishing a baseline XRF of which chemical or chemicals bind to a type of receptor signal for a heavy element in each portion or aliquot of each referred to in the art as a "druggable target, how strongly they protein, and then exposing the protein to conditions that may bind, whether or not they bind selectively (i.e. whether or not result in protein modification. Afterward, the XRF signal due they also bind undesirably to other receptors), and for those to the heavy element would be measured. The baseline X-ray that bind selectively to what degree the selectivity is. After fluorescence signal is then Subtracted from this measured identifying a drug that binds strongly and selectively to a XRF signal, and the difference is the “net XRF signal'. The desired druggable target, the drug is synthesized in large net XRF signal would be standardized by dividing by the quantities. amount of the receptor in the portion being tested. The stan 0101 The invention can be used to estimate the binding dardized XRF signals may then be compared. selectivity of a chemical to one or more receptors under 0105. This invention may be used to estimate the thera different conditions. For example, the binding affinity of a peutic index of a chemical/drug/analog. The therapeutic chemical in one solution can be compared to its binding index is a measure of drug selectivity that is ordinarily calcu affinity in a different solution. The chemical would include lated from data obtained from experiments with animals. The one or more heavy elements. The effect that other compo therapeutic index of the drug is typically defined as the ratio nents that do not have a heavy element in either solution have of two numbers, LD50/ED50, where LD50 is the dose of a on the binding affinity of the chemical could be inferred by drug that is found to be lethal (i.e. toxic) for 50 percent of the observing any observed differences in binding affinity of the population of animals used for testing the drug, and ED50 is chemical. the dose of the drug that is found to have a therapeutic effect 0102 Some aspects of the invention are related to person for 50 percent of that population. More broadly, it is a mea alized medicine, and involve estimating the relative effective sure of the how much of the drug is needed to produce a ness of two or more drugs. This may involve, for example, harmful effect relative to the amount needed to produce a estimating the binding selectivities of two (or more) drugs to beneficial effect. The ratio LD50/ED50 is therefore, a mea two (or more) receptors. The receptors may be proteins or sure of the approximate “safety factor” for a drug; a drug with other biological ligands, typically derived from a medical a high therapeutic index can presumably be administered patient or a participant in a clinical drug trial. For medical with greater safety than one with a low index. The invention patients, there may be a question about which drug to use to may be used to provide an estimate of the therapeutic index treat the patient, and the invention can be used to guide the by, for example, measuring the binding affinity of a chemical doctor toward prescribing a specific drug for treatment. For to a receptor associated with side effects and to a receptor applications related to personalized medicine, these types of associated with efficacy. The ratio of the measured binding drugs would include at least one heavy element. For drugs affinities (efficacy divided by side effects) provides an esti that are being compared, the drugs might include the same mate of the “therapeutic index. For an example of using heavy element, or different heavy elements. Each drug may DNA arrays with optical fluorescence high-throughput be a single chemical, or may be a mixture of chemicals. If the screening to estimate a therapeutic index, see R. Ulrich and S. US 2008/0220441 A1 Sep. 11, 2008 62

H. Friend, “Toxicogenomics And Drug Discovery: Will New the true positive relative to the false positive, which is related Technologies Help Us Produce Better Drugs?’ Nature to the accuracy of the medical test. Reviews Drug Discovery, vol. 1, pp. 84-88 (2002), incorpo 0110 Diagnostic tests that use standard immunoassay rated herein by reference. methods require fluorescently-tagged chemicals. It has been 010.6 An example relating to the use of the invention to previously pointed out that it is generally assumed that the obtain a simple estimate of a therapeutic index may involve attachment of a fluorescent tag to a chemical only serves to exposing an array of the proteins 5HT2A and NAa1 to a make visible the otherwise invisible chemical, and does not solution of olanzapine. Assuming that the 5HT2A and NAa1 alter its binding properties. However, Small changes to the structure of a chemical could affect its function, so this of the array are present in equal amounts, the net sulfur XRF assumption that tagged chemicals have the same binding signal due to the olanzapine should be between 1.6 and 20 affinity and selectivity as their untagged counterparts may not times higher for olanzapine bound to 5HT2A than for olan be a valid one. The tagged chemicals are structurally different Zapine bound to NAa1. from their untagged counterparts, and these structural differ 0107 Another example relating to the use of the invention ences could affect their binding affinities and selectivities. to obtain an estimate of a therapeutic index is now described. Since binding affinities and selectivities derived using tagged A therapeutic index for a non-steriodal anti-inflammatory chemicals are suspect, the binding properties of receptors and drug (commonly referred to as an “NSAID) may be obtained chemicals should be evaluated using the untagged chemical by exposing an array that includes the proteins COX-1 and or receptor and not with a tagged chemicals. This is not COX-2 to a solution of meloxicam. Assuming the COX-1 and possible with standard immunoassay methods, which require COX-2 are present in equal amounts, the net XRF signal due fluorescently-tagged chemicals. By contrast, the present to sulfur in the meloxicam should be about 10 times higher for invention allows an existing, untagged chemical (or analog or meloxicam bound to COX-2 than for meloxicam bound to drug) to be used as the probe molecule. COX-1. 0111. An example of using the invention for a diagnostic 0108. Yet another example relating to the use of the inven test for inflammation, for example, may include exposing tion to obtain an estimate of a therapeutic index may involve spatially separated proteins to a drug. Spatially separated exposing an array that includes COX-1, COX-2, and proteins proteins, for example COX-1 and COX-2 derived from a derived from hepatocytes, to a solution of meloxicam. blood sample from a patient, may be exposed to the drug Assuming the COX-1 and COX-2 are present in equal meloxicam. The binding affinities of meloxicam to COX-1 amounts, the net XRF signal due to the sulfur in the meloxi and COX-2 are known. Therefore, the net XRF signal due to cam should be about 10 times higher for meloxicam bound to sulfur in the meloxicam that is bound to COX-1 versus that for COX-2 than for meloxicam bound to COX-1. Any XRF signal COX-2 may indicate the relative amounts of COX-1 and due to sulfur in meloxicam bound to hepatocyte-derived pro COX-2 in the blood sample. teins may suggest that the meloxicam may concentrate in the 0112 The invention may also be used to develop optically liver and may be cause for further analysis of the toxicity of fluorescent immunoassay diagnostics by comparing the meloxicam. selectivity of a non-fluorescently tagged chemical to a fluo rescently-tagged chemical. XRF would be used to determine the binding selectivity of the non-tagged chemical, and either CH3 XRF or optical fluorescence would be used to determine the binding selectivity of the tagged chemical. If the selectivities OH O S N of the tagged and untagged chemicals are proven to be simi lar, then the tagged-chemical may be used as the diagnostic N N us N H with the expectation that its binding properties are acceptably N similar to those of its untagged counterpart. s1 NCH, 0113 Binding selectivity information provided by the M \, present invention is also important for uses related to Mate O O rials Science. Binding selectivity information can be used, for Meloxicam example, in designing high performance water filters, such as water filters that remove contaminants such as lead, arsenic, 0109 Binding selectivity information provided by the arsenate anions, or pesticides, from contaminated water. invention is important for understanding the properties of Water filters can be manufactured with receptors that have a drugs. It is also important for other applications such as for high affinity for a particular contaminant (lead, for example) medical diagnostics. For medical diagnostics, the ratio of the and a low affinity for other contaminants (iron, for example) binding affinity of probe molecules (i.e. molecules that selec in the contaminated water. By passing the contaminated water tively bind to proteins associated with a particular disease) for through this filter, the lead is removed while the iron isn’t. The a disease marker (i.e. a protein in a biological sample, Such as beneficial effect of not removing the iron is that the iron, a blood or sputum sample, from a patient having that disease, which is present in much larger amounts than the lead is, does which indicates that a disease is present) vs. the binding not overload the filter as the contaminated water is being affinity of probe molecules for other proteins not associated treated. Overloading would mean that the filter would have to with that disease, is related to the accuracy of a medical test. be replaced often. If the probe molecules bind to the disease marker, then the 0114. The binding selectivity, i.e. the ratio of binding medical diagnostic test provides a true positive result. How affinity of a chemical to one receptor versus the binding ever, when the probe molecules bind to other proteins besides affinity to a different receptor, may be performed as follows. the disease marker, then the medical diagnostic test provides First, a baseline X-ray fluorescence is obtained. This baseline a false positive result. The above ratio provides a measure of may be obtained by, for example, measuring the X-ray fluo US 2008/0220441 A1 Sep. 11, 2008

rescence (XRF) signal due to a particular element from each ment of the excited atoms does not have a significant effect on receptor in the absence of any added chemical. This is an the XRF signal. Atoms are not degraded like chemical func empirical measurement that establishes the baseline XRF tional groups, so photobleaching does not occur in XRF. signal for that element for each receptor. Alternatively, the 0117. When the chemical binds to a localized receptor, the baseline XRF can be calculated for each receptor. This cal chemical also becomes localized. In order to maximize the culation requires knowledge of the amount of that element XRF efficiency, it is preferable that the dimensions of the that is present in the receptor and a calibration factor to receptor match those of the spot generated by the excitation convert an amount of that element into an XRF intensity beam. signal; the amount of the element believed to be present may then be multiplied by the calibration factor to provide a cal 0118 For expensive receptors, it is preferable that the culated XRF signal. The calibration factor may be obtained sample of receptor be as small as possible. It is therefore by measuring a set of standards containing that element, and preferable that the receptor sample belocalized within an area calculating the signal as a function of the amount of the about 1 mm or less, and within a volume of 1 mm or less. element. Preferably, the XRF baseline is a measured baseline. 0119 When multiple receptors are being tested, they are 0115 For cases where there is a low probability that there each deposited in separated portions on a Substrate. The por is an element in common between the receptor and the chemi tions are spatially separated from each other so that the XRF cal and where that element is used for the XRF measurement, excitation beam excites only one portion, and any chemical a foreknowledge of the composition of the receptor(s) may be bound to the portion of receptor, at a time. sufficient. For obtaining the XRF baseline for a set of organic I0120 Receptor arrays such as analytical protein arrays, receptors that are being screened for their binding affinities functional protein arrays, analytical DNA arrays, functional for a metal (e.g. lead) or for a chemical that has XRF-mea DNA arrays, analytical RNA arrays, functional RNA arrays, Surable chemical elements (e.g. phosphorus, chlorine) that are known not to be present in the set of organic receptors, for arrays derived from clinical patients, arrays derived from example, the baseline XRF signal of the receptors may be participants in clinical trials, tissue samples, tissue arrays, calculated or assumed to be negligible. For a Sulfur-contain cellular arrays, and cellular samples may be used with the ing receptor (e.g. avidin) and a phosphorus-containing present invention. These and other types of arrays have been chemical (e.g. biotin-DHPE, or N-(Biotinoyl)-1,2-dihexade described in detail in the following papers: H. Zhu and M. canoyi-sn-glycero-3-phosphoethanolamine triethylammo Snyder, “Protein Chip Technology (Review). Current Opin nium salt), for example, the XRF signal of phosphorus from ion in Chemical Biology, vol. 7, pp.55-63, (2003); G. Mac the avidin may be assumed to be negligible, and any phos Beath and S. L. Schreiber, “Printing proteins as microarrays phorus XRF signal measured may be assumed to be due to the for high-throughput function determination. Science, Vol. biotin-DHPE. 289, pp. 1760-1763, (2000); E. T. Fung et al., “Protein bio 0116. A receptor is preferably localized and separated chips for differential profiling. Current Opinion in Biotech from other receptors. Localization concentrates the receptor nology, Vol. 12, pp. 65-69, (2001); T. Kukar et al., “Protein and any chemical bound to the receptor, therefore improving Microarrays to Detect Protein-Protein Interactions Using Red the sensitivity of the XRF technique. This sensitivity and Green Fluorescent Proteins.” Analytical Biochemistry, improvement due to localization for XRF contrasts with other vol.306, pp. 50-54, (2002); G.Y. J. Chen et al., “Developing techniques, such as optical fluorescence. Optical fluorescence a Strategy for Activity-Based Detection of Enzymes in a may be affected by fluorescence quenching, fluorescent reso Protein Microarray.” ChemBioChem, pp. 336-339, (2003); K. nance energy transfer, photobleaching, and the like. Fluores Martin et al., “Quantitative analysis of protein phosphoryla cence quenching diminishes the optical signal and therefore tion status and protein kinase activity on microarrays using a decreases sensitivity. Fluorescence resonance energy transfer novel fluorescent phosphorylation sensor dye.” Proteomics, alters the wavelength of the fluorescence signal. Photobleach Vol. 3, pp. 1244-1255, (2003); J. Burbaum and G. M. Tobal, ing degrades the fluorescence signal over time and exposure “Proteomics in drug discovery. Current Opinion in Chemi to light. By contrast, XRF is not subject to fluorescence cal Biology, Vol. 6, pp. 427-433. (2002); I. A. Hemmila and P. quenching because the energy differences between the Hurskainen, “Novel detection strategies for drug discovery.” ground state and the excited states are much greater for XRF Drug Discovery Today, Vol. 7, pp. S150-S156, (2002). The than for optical fluorescence. Energy loss via optical fluores arrays described in these papers may be used with the present cence may occur through non-radiative pathways that do not invention. produce an optical signal. XRF Sometimes is subject to fluo I0121. In order to allow mass transport of a chemical to all rescence resonance energy transfer (see, for example, J. Sher parts of a receptor deposited on an area of the Substrate, it is man, Spectrochimica Acta, vol. 7, pp. 283-306 (1955)), incor preferable that there be some inhomogeneity of the receptor porated by reference herein). Optical fluorescence usually in that deposited area. Regarding the inhomogeneity of the requires an unsaturated functional group (a carbonyl group, a deposition, the amount of receptor on a 1 square micron dienyl group, an aromatic group, etc.) with an electron that portion of the deposited area should be different from the can be excited from the ground electronic state to an excited amount of receptor on another 1 square micron portion by at state with non-ionizing radiation (ultraviolet, visible, and least 10 percent. An alternative way of comparing the amount near-infrared radiation). This excitation forms a reactive elec of inhomogeneity of deposited receptor on an area involves tron-hole pair that can chemically react with neighboring measuring the amount of chemical in each 1 Square micron molecules, or within the same molecule. This chemical reac pixel within the deposited area, finding the average amount of tion degrades the optically fluorescent chemical functional the chemical per square micron over the entire deposited area, groups, which diminishes the optical fluorescence during and calculating the standard deviation of the amount of the degradation. In contrast, XRF employs ionizing radiation for chemical per square micron pixel. The standard deviation of exciting inner core electrons of atoms. The chemical environ the amount of the chemical per pixel divided by the average US 2008/0220441 A1 Sep. 11, 2008 64 amount of the chemical per square micron of area should be peutic index are obtained when the chemical is in an environ greater than about 0.1% and preferably greater than about ment that more closely approximates biological conditions. 19/6. An example of such an environment is a buffered solution that 0122 Receptors may be inhomogeneously deposited by contains chemicals that are typically found in biological attaching the receptors to polystyrene beads, for example. organisms (e.g. blood-borne ligands). The points of attachment on polystyrene beads are random I0127. For medical purposes, such as the development of and non-uniform. The attachment of receptors to beads is new therapeutic chemicals (i.e. drugs), the ratio of the binding described in U.S. Patent Application 20030027129 entitled affinity of a chemical to the target receptor versus the binding “Method for Detecting Binding Events. Using Micro-X-ray affinity of that chemical to one or more other receptors (which Fluorescence Spectrometry,” which was published on Feb. 6, is an estimate of the therapeutic index according to the present 2003, which describes the use of beads that were about invention) is important to know. It is also important to know 80-120 micrometers in diameter, with an average diameter of the binding affinity and the therapeutic index estimate of the about 100 micrometers. chemical for these receptors in typical chemical environ 0123. The measured binding affinity of a chemical to a ments and in the presence of common biological ligands. The receptor depends on the chemical environment and tempera binding affinity may be measured in the presence of for ture. More specifically, the binding affinity of a chemical to a example, blood-borne proteins, ligands, fats, triglycerides, receptor does not change when the chemical environment and fatty acids. These proteins and ligands may function as a does not change. External factors, however, may have an proxy for distribution of the chemical between the circulatory effect on the measured binding affinity. system and cells. Fats, triglycerides, and fatty acids may 0.124. The free energy of binding of a chemical to a recep function as a proxy for the distribution of the chemical tor may be represented by the following equation: between fat cells (or cell membranes) and the target receptor, AG=AH-TAS as well as for passive transcellular transport. I0128. Another aspect of the present invention is related to where AG is the change in the Gibbs free energy of the determining whether or not a first chemical and a second binding reaction, AH is the change in enthalpy of the binding chemical have similar selectivity for binding to each of a reaction, T is the temperature, and AS is the change in entropy plurality of receptors. For example, if a baseline is obtained of the binding reaction (see, for example: Gordon M. Barrow, for receptor 1 and receptor 2, and then if chemical A and Physical Chemistry, 5" Ed., McGraw-Hill, NY, 1988, Chap chemical B and chemical C are exposed to receptor 1 and ter 7). The temperature should be constant to avoid changing receptor 2, and the baseline is subtracted from the XRF sig the TAS term, because changes to the TAS term would intro nals after exposure, the similarity of the binding selectivities duce temperature derived artifacts into the measurements. AG can be assessed. For this example, chemical A and chemical B will also be affected by, for example, the presence of materials are both are selective for Receptor 1 versus Receptor 2 by that coordinate to the receptor and/or chemical. Bonds that about an order of magnitude, while chemical C is not selective form between these materials and the receptor and/or chemi for Receptor 1 versus Receptor 2, as shown in TABLE 2 cal must be broken before the chemical can bind to the recep below. tor. Energy is required to break these bonds, and this energy will be factored into AG of the equation, and will make AG of binding between the chemical and receptor appear Smaller TABLE 2 than it actually is. Therefore, in order to obtain binding affini Receptor 1 Receptor 2 ties for a chemical with multiple receptors, the chemical Chemical A 10 1 environment for the receptors and chemicals should not Chemical B 11 1 change. In addition, the temperature should not vary between Chemical C 1 1 measurements and all measurements should be taken at Sub stantially the same temperature, i.e. within +3°C., and more preferably within +1° C. I0129. This aspect of the invention may be exemplified 0.125 For drug development, the chemical environment with specific receptors having known properties. For preferably approximates that of the physiological environ example, Receptor 1 may be exemplified by COX-1 (inhibi ment. Useful drugs should perform optimally at, or near, tion of which is associated with intestinal ulcers) and Recep physiological temperatures. One aspect of this invention is tor 2 may be exemplified by COX-2 (inhibition of which is related to determining binding selectivities at or near the associated with anti-inflammation). temperature of the body, which is about 37 degrees Celsius. I0130 TABLE3 below includes selectivity data for sample Preferably, the exposure of receptors to chemicals/analogs/ canine COX-1 and COX-2 (see, for example: Christopher drugs according to this invention is typically performed at a Jones, Practical COX-1 and COX-2 Pharmacology: What's it temperature of from about 15 degrees Celsius and about 45 All About?” which can be found at the website http://www. degrees Celsius, and more preferably is between 32 degrees vetmedpub.com/cp/pdf/symposium/nov 1.pdfl. Celsius and 42 degrees Celsius, and most preferably at a temperature of about 37 degrees Celsius. TABLE 3 0126 Useful drugs should also perform optimally in the presence of other, potentially interfering chemicals that are COX-1 COX-2 also present in a physiological environment. The therapeutic Celecoxib 1 9 Meloxicam 1 10 index provides an estimate of the performance of a drug. Ketoprofen 1 .6 Simple estimates of a therapeutic index may be obtained for New Drug (goal) 1 >10 a chemical in a solution that does not contain potentially interfering chemicals. More realistic estimates of the thera US 2008/0220441 A1 Sep. 11, 2008

0131 TABLE3 compares the selectivity of CELECOXIB, relates to XRF data obtained for the receptor labeled receptor MELOXICAM, and KETOPROFEN for the receptors 5.2. The Pb XRF intensity of receptor 5.1 is 2295, the FeXRF COX-1 and COX-2. According to TABLE 3, CELECOXIB intensity, is 505, and the ratio of Pb XRF intensity to the Fe has a selectivity of 9 to 1 in favor of COX-2 versus COX-1, XRF intensity, which indicates the selectivity of receptor 5.1 and MELOXICAM has a selectivity of 10 to 1 also infavor of for binding to lead versus binding to iron, is 4.54. Similarly, COX-2 versus COX-1, while KETOPROFEN has a selectiv the Pb XRF intensity for receptor 5.2 is 13092, the Fe XRF ity in favor of COX-1 versus COX-2 of only 1 to 0.6. Drug intensity is 252, and the ratio of the Pb XRF intensity to the Fe development involves finding/developing new drugs that XRF intensity is 51.95. The ratio of 51.95 to 4.54, which have Superior selectivities (i.e. Superior therapeutic indices) equals 11.4, indicates that receptor 5.2 is 11.4 times as selec Versus existing drugs. The discovery/development of more tive for lead than receptor 5.1 is. selective drugs than those shown in TABLE 3 may involve 0.136 For drug development, it is desirable to understand measuring the selectivity of a new drug and comparing its how the drug will bind to a receptor. Drug development may selectivity to that of the more effective drugs e.g. CELE involve systematically varying the chemicals being tested for COXIB. The goal would be to develop a new drug with their affinities to one or more receptors, in order to optimize superior selectivity for COX-2 over COX-1 as compared to the binding affinity of one of these chemical analogs to a CELECOXIB. desired receptor and to optimize the therapeutic index, i.e. the 0132 A new drug should be at least one percent more ratio of the affinity of the chemical to a desired receptor to the selective, and more preferably more than 5 percent more affinities of that chemical to undesired receptors. This sys selective than an existing, effective drug. tematic variation of chemicals for drug development is some 0133. An example that demonstrates how the present times referred to as a drug development analog program. The invention may be used to provide information related to the development of a potential new drug using analogs and XRF selectivity of a plurality of receptors to a chemical is now according to the present invention involves determining the described. The chemical is the lead ion. For this example, a binding affinity of a potential drug to multiple receptors, and library consisting of 400 tripeptide receptors was prepared by comparing these binding affinities to provide selectivity split-pool synthesis. Each receptor of the library was information. This process is completed for a first chemical, covalently attached to a spherical polystyrene resin particle. and then completed for a second chemical that is an analog of The particles had an average size of about 100 microns. The the first chemical. Then the binding affinities and selectivities library of receptors was exposed to an aqueous solution, for the first chemical and for its analog are compared to having a pH of 7, of lead nitrate (7 mM). A portion of the determine which of the two is the more selective. This may library of receptors was then analyzed by XRF. The XRF involve mixing the first chemical with one or more receptors, intensity and relative binding affinity of three of the receptors allowing a receptor-chemical complex to form, and then mea for lead ion are shown in TABLE 4 below. Suring the amount of receptor-chemical complex formed using XRF, then repeating these steps with the analog. Any TABLE 4 complexes that form with the analog would also be measured by XRF. This may be repeated with additional analogs of the Receptor Pb XRF Signal Relative Binding Affinity first chemical. Receptor 4.1 991.93 111919349 0.137 There are several criteria that may be used to deter Receptor 4.2 924.94 1.04360875 mine whether chemicals are analogs of the first chemical. One Receptor 4.3 886.29 1 criterion is whether the first chemical and another chemical have one or more properties in common. The similarity may 0134. Another example that demonstrates how the present be determined by computational modeling, such as a "Quan invention may be used to provide information related to the titative Structure Activity Relationship' (QSAR, see, for selectivity of a plurality of receptors to two chemicals is now example: R. Perkins et al., “Quantitative Structure-Activity described. The two chemicals are the leadion and the ironion. Relationship Methods: Perspectives on Drug Discovery and For this example, a library consisting of 400 tripeptide recep Toxicology. Environmental Toxicology And Chemistry, Vol. tors was prepared by split-pool synthesis. Each receptor of the 22, pp. 1666-1679 (2003); and T. W. Schultz et al., “Quanti library was covalently attached to a spherical polystyrene tative Structure-Activity Relationships (QSARs) in Toxicol resin particle. The particles had an average size of about 100 ogy: a Historical Perspective” THEOCHEM, vol. 622, pp. microns. The library of receptors was exposed to an aqueous 1-22 (2003), both incorporated by reference herein). solution (pH 7) of lead nitrate (7 mM) and iron nitrate (7 mM). 0.138 QSAR models compare the charge, polarity, hydro A portion of the receptors was then analyzed by XRF. The gen-bonding donor/acceptor pattern, lipophilicity, Volume, XRF intensity and relative binding affinity of two of the and other properties of chemicals to determine whether two or receptors for lead ion and iron ion are shown in TABLE 5 more chemicals are likely to have similar binding properties below. for a receptor. 0.139. Another criterion for determining whether two TABLE 5 chemicals are analogs of each other relates to whether the two Pb XRF Intensity/ chemicals have a common functional group and where that Pb XRF Intensity Fe XRF Intensity Fe XRF Intensity functional group is attached. The following clarifies what is meant by the term analog. Benzene, methylbenzene, ethyl Receptor 5.1 2295 505 4.54 benzene, isopropylbenzene, and n-propylbenzene, for Receptor 5.2 13092 252 51.95 example, are analogs of each other. Olanzapine and trifluo romethylolanzapine are analogs of each other. Methyl salicy 0135. The first entry of TABLE 5 relates to data obtained late, ethyl salycylate, phenyl salicylate, N-methyl salicyla for the receptor labeled receptor 5.1, and the second entry mide, N,N-dimethylsalicylamide, and salicylic acid are US 2008/0220441 A1 Sep. 11, 2008 66 analogs of each other. The aromatic compounds 4-chlorotolu date may have a different receptor affinity or selectivity than ene, and 3-chlorotoluene are analogs of each other. Cyclo participants that respond positively to the drug candidate. pentane, cyclohexane, and cycloheptane are analogs of each 0145 One aspect of the invention may be demonstrated other. Benzene, pyridine, and thiophene are analogs. Ethyl using an array prepared as described in Kukar et al., “Protein benzene and methoxybenzene are analogs of each other. Microarrays to Detect Protein-Protein Interactions Using Red Ethyl benzene, ethenyl benzene (i.e. styrene), and ethynyl and Green Fluorescent Proteins.” Analytical Biochemistry, benzene (i.e. phenyl acetylene) are analogs of each other. vol.306, pp. 50-54 (2002). The baseline sulfur content of the More generally, enantiomers of a chemical are analogs of receptors of the array would be measured using X-ray fluo each other, diastereomers are also analogs of each other. rescence spectroscopy. Afterward, the receptors of the array would be exposed to a solution of olanzapine, which has the 0140. A third criterion for determining whether two structural formula chemicals are analogs is related to whether the two chemicals share atoms having the same connectivity, where the term connectivity is meant to describe the shortest path of atoms CH that connect two functional groups. For example, 1,2-dichlo /-3 robenzene and 1,2-dinitrobenzene have the same connectiv ity between the two functional groups; the connectivity r N between the chlorine groups in the chemical 1,3-dichloroben 2 Zene is the same as the connectivity between the two nitro NS groups in the chemical 1.3-dinitrobenzene. 0141 Preferably, a chemical being tested for binding with -( ) a receptor according to the present invention includes at least I S CH3 one chemical element having an atomic number of nine or H higher. Excitation photons used with the present invention Olanzapine should have energies of at least 300 eV. The excited atoms should have a fluorescence half-life of 10 ns or less. The importance of having Such a short fluorescence lifetime is and the chemical formula C7HoNS (olanzapine is the related to the “dead time', which is a period of time after the active ingredient in ZYPREXAR). Afterward, the sulfur con X-ray fluorescence is measured. No additional X-ray fluores tent of each receptor would be measured again using X-ray cence can be measured during the dead time. Preferably, the fluorescence microscopy. The difference in sulfur content fluorescence lifetime of the type of atom being measured between the two measurements is related to the binding of should be less than the dead time of the detector. More pref olanzapine to receptors the array. erably, the fluorescence being measured should have a fluo 0146 It is believed that the therapeutic effects of olanza rescence half-life of 10 nanoseconds (ins) or less, and most pine are a result of olanzapine binding to several receptors, preferably the fluorescence being measured should have a including the human serotonin 5HT2A receptor (see, for half-life of 100 picoseconds (ps) or less. example: http://www.gpcrorq). Toxic effects are believed to 0142. If a mixture of chemicals, as opposed to a single occur as a result of olanzapine binding to alpha-1-adrenergic chemical, is used, only one of the chemicals is required to (NAa1) receptors (see, for example: “Olanzapine have a heavy element. If more than one has a heavy element, (ZyprexaR) in Clinical Toxicology Review, Vol. 18, no. 2, and the heavy element is the same element, then a baseline March 1997. The pKi (where pKi=-log Ki, where Ki is the XRF measurement of the binding affinity of each of the inhibition equilibrium constant) of olanzapine for 5HT2A is chemicals with that element to one or more receptors should reported to be 7.8-8.9, while the pKi of olanzapine for NAa1 be obtained. The measurements may be obtained sequen is reported to be 6.3-7.6. If the binding of the chemical to a tially, e.g. by measuring the XRF spectrum of each receptor of receptor also inhibits that receptor, then the pKa and the pKi an array, then exposing the receptors of the array to a chemi of the chemical have the same value. cal, then measuring the XRF spectrum of the array after 0147 The selectivity of binding of olanzapine to NAa1 exposure to the chemical, then adding another chemical, then versus 5HT2A may be measured by first preparing an array of measuring the XRF spectrum of the array after exposure to NAa1 and 5HT2A on a substrate, then measuring the baseline the other chemical. This process may be repeated for as many Sulfur content of each enzyme using XRF, then contacting the chemicals as desired. arrayed enzymes with a solution of olanzapine, and then 0143. After measuring binding affinities between recep measuring the total amount of Sulfur using XRF, and then tors and chemicals, the receptors may be analyzed in terms of subtracting the baseline amount of sulfur from the total any of their particular structural of functional features than amount of Sulfur, which indicates the amount of olanzapine may promote binding or inhibit binding. A variety of analyti that binds to each enzyme. cal techniques useful for performing this type of analysis 0.148. From the binding data obtained for olanzapine, it include spectroscopy (e.g. infrared spectroscopy, fluores appears that chemicals useful as drugs form a complex with at cence spectroscopy), spectrometry (e.g. mass spectrometry, least one receptor that has a pKi of greater than 5. nuclear magnetic resonance spectrometry, Surface plasmon 0149 According to the invention, the X-ray excitation resonance), functional assays, and the like. beam is used to excite one receptor at a time. The temperature 0144. The binding properties of a receptor to a chemical of the array should be kept constant so that each X-ray mea may be correlated with a positive, or with an adverse, Surement is performed at the same temperature, or at nearly response of an animal, clinical trial participant, or medical the same temperature (+3 degrees Celsius). For the case of patient. For the case of clinical trial participants, for example, measuring the binding of olanzapine to each receptor, for those participants who respond adversely to the drug candi example, each measurement should be performed at the same US 2008/0220441 A1 Sep. 11, 2008 67 temperature or at nearly the same temperature because the time. Preferably the contact times between the first solution binding affinity changes as the temperature changes. and the receptor and the second solution and the receptor are 0150. After the selectivity of the olanzapine for binding to the same. 5HT2A and to NAa1 is measured, additional chemicals can 0155 The method may also be practiced using a solution be similarly measured in order to determine whether any having a concentration is gradient; using a concentration other chemical has a better selectivity for 5HT2A versus gradient is similar to using two solutions at two different NAa1. A chemical such as the trifluoromethylolanzapine, times. The reaction kinetics may then be determined, as which has the structural formula described in Gordon M. Barrow, Physical Chemistry, 5" Ed., McGraw-Hill, NY, 1988, chapter 18. The activation param eters AG, AH, AS may be determined using the Arrhenius equation (see, for example: Gordon M. Barrow, Physical Chemistry, 5' Ed., McGraw-Hill, NY, 1988, pp. 710-712.) and the Eyring equation (see, for example: Gordon M. Bar N row, Physical Chemistry, 5' Ed., McGraw-Hill, NY, 1988, NS pp. 756-757.) 0156 This aspect of the invention may be demonstrated by preparing a protein array that includes at least one protein receptor (see, for example: Kukaret al., “Protein Microarrays I S CF to Detect Protein-Protein Interactions. Using Red and Green H Fluorescent Proteins.” Analytical Biochemistry, vol. 306, pp. trifluoromethylolanzapine 50-54 (2002), incorporated herein by reference). The baseline sulfur content of the protein spots of the array is determined for example, may be screened against the same receptor array, using X-ray fluorescence spectroscopy. After determining the or screened against another receptor array having the same baseline Sulfur content, the protein array is contacted with a proteins, and the binding selectivity for trifluoromethylolan solution of olanzapine. Afterward, the sulfur content of each Zapine can be measured. If the selectivity of trifluoroolanza protein spot is determined again using X-ray fluorescence pine for 5HT2A versus NAa1 is greater than the selectivity of microscopy. The difference in sulfur content between the two olanzapine is, then trifluoromethylolanzapine would be measurements for each protein spot is then quantified. This expected to be a superior drug. difference is related to the binding of olanzapine to proteins in 0151. Another aspect of the present invention relates to the the array. determination of the kinetic parameters of an interaction 0157. In order to measure the rate of binding of olanzapine between a chemical and a receptor. to 5HT2A, a solution of olanzapine may be contacted with a 0152. After the baseline is measured or calculated for a 5HT2A. The 5HT2A may be in solution, or as part of an array receptor, as previously described, the receptor is exposed to a of proteins, or associated with a substrate. If the 5HT2A is in chemical at a particular temperature. The temperature is pref Solution, it should be immobilized in Some manner, such as in erably a fixed temperature, preferably between about 27 the manner described in U.S. patent application Ser. No. degrees Celsius and about 47 degrees Celsius and more pref 10/621,825 entitled “Method and Apparatus for Detecting erably is a fixed temperature between about 32 degrees Cel Chemical Binding”. Any increase in the sulfur XRF signal, sius and about 42 degrees Celsius. The XRF signal of any which is presumably due to an increase in the amount of receptor-chemical complex formed is then measured. After olanzapine that is bound to 5HT2A, may be measured peri taking this measurement at a first fixed temperature, the tem odically over time to determine the rate at which olanzapine perature is adjusted so that it is different from the first tem binds to 5HT2A. This may be repeated using solutions having perature by at least 2 degrees Celsius. The XRF signal should various concentrations of olanzapine, and at different tem then be measured for the sample at this new temperature. peratures in order to determine the rate of binding at different 0153. Alternatively, the first measurement and second temperatures; this is important for determining the activation measurement can be performed as follows. The receptor and parameters AG, AH, AS, as well as for determining the chemical can be mixed first at one temperature, and next at a binding kinetics that would be expected for a healthy patient different temperature. Then, the chemical-receptor com (37°C.) versus a patient with a mild (38°C.) or severe (>38° plexes that form are isolated (e.g. by spatially separation) so C.) fever. that any chemical that was bound to the receptor remains 0158 For examining a chemical that is a candidate for spatially associated with the receptor. The XRF measure drug discovery according to the present invention, it is pref ments may then be obtained at any temperature desired. erable that the chemical has one or more features that have 0154 The kinetic parameters for the formation of a recep come to be known as “Lipinski’ features, described in C. A. tor-chemical complex may similarly be determined by Lipinski et al., “Experimental And Computational obtaining the baseline XRF signal for at least one receptor as Approaches To Estimate Solubility And Permeability In Drug described above, followed by exposing the receptor to a first Discovery And Development Seftings.” Advanced Drug solution of a chemical where the chemical is present in a fixed Delivery Reviews, Vol. 23, pp. 3-25, (1997). These features concentration. The XRF signal of any chemical-receptor include the following: a molecular weight equal to or less than complex is then measured. These steps are then repeated with about 500 daltons; a number of hydrogen bond acceptors that a second solution having a different concentration of the is equal to five or less; a number of hydrogen bond donors that chemical. The contact times between the first solution and the is equal to ten or less; and a logP offive or less where P is the receptor and the second Solution and the receptor are mea ratio of the solubility of the chemical in octanol to the solu sured in order to determine the rate of the binding reaction, bility of the chemical in water. Elaborating on the hydrogen which is related to the amount of complex formed per unit bond acceptor properties of drug candidates, it is preferable US 2008/0220441 A1 Sep. 11, 2008

that the chemical has the property that the Sum of nitrogen, decrease the number of adverse drug reactions, which cur oxygen, Sulfur, fluorine, chlorine, bromine, and iodine groups rently result in the deaths of about 100,000 hospitalized available for hydrogenbonding in the chemical is five or less. patients per year, and cause serious side effects in another 2.2 For the purposes of counting hydrogen bond acceptors, each million people. Personalized medicine currently relies on of the following is counted as a single hydrogen bonding genotyping a patient in order to guide the physician in admin acceptor: difluoromethyl groups, trifluoromethyl groups, istering drugs to the patient. This genotyping focuses on dichloromethyl groups, trichloromethyl groups, dibromethyl single nucleotide polymorphism (SNP) analysis. The cost per groups, tribromethyl groups, ester groups, amide groups, car SNP analysis currently is about 1 dollarper SNP, but with the boxylic acid groups, urea groups, and carbamate groups. Also current poor understanding of pharmacogenomics and the for the purposes of counting hydrogen bond acceptor groups, large number of possible SNP's (thousands), it is believed that the following are not counted as a hydrogen bond acceptor: costs related to SNP analysis must decrease to pennies per nitro groups, nitroso groups, and cyano groups. SNP before SNP analysis becomes more widely used. The 0159. While the Lipinski features suggest that a molecular analysis provided using the present invention, by contrast, weight of less than about 500 is preferable, Hemmila (vide allows phenotyping and direct analysis of drug interactions infra) reported that chemicals having a molecular weight of with protein profiles, thus providing higher quality informa 5000 daltons or less cannot be tagged with an optical tag tion about the particular patient and disease without overly perturbing their binding properties, such as 0166 Thus, the present invention may be used in person binding affinities (see I. A. Hemmila and P. Hurskainen, alized medicine to assist physicians in prescribing drugs for “Novel detection strategies for drug discovery.. Drug Dis their patients. A protein array, such as an array on a commer covery Today, Vol. 7, pp. S150-S156, (2002)). The present cially available protein chip manufactured by CiphergenTM or invention does not employ tags and thus can be used for ZyomyxTM, for example, may be exposed to protein extracts studying the binding of chemicals that have a molecular from a cancer patient. In this case, as in others where there is weight of 5000 daltons or less. a clear difference between diseased tissue and healthy tissue, 0160 For a chemical having hydrogen bond donor groups, extracts from the tumor and from healthy tissue would be it is preferable that the chemical has the property that the sum taken from the patient. After exposing the chip to the extracts, of hydrogen atoms bound to Sulfur, nitrogen, and oxygen in a baseline XRF baseline spectrum would be obtained. Solu the chemical is ten or less. tions of each drug that the doctor is considering for treating 0161 For drug candidates, it is preferable that chemical is the tumor would then be contacted with the protein chip. The soluble in water. The chemical should be dissolved in a fluid binding affinity of each drug would then be measured accord that includes water, preferably with a pH of from about pH 6 ing to the invention, which involves measuring the XRF sig to about pH 8. nals for heavy elements present in the drug-receptor complex, 0162 The chemical may have Zero, one, or more than one Subtracting out the baseline from this measurement, and then chiral center. A chemical sample that contains equal amounts comparing the signals to see which drug exhibits a more of each enantiomer may be used. Once it has been determined selective binding to the tumor versus the healthy tissue and/or using the invention that the chemical binds to a receptor, the which drug binds more strongly to the tumor. chemical may be analyzed to determine which particular 0167. The efficacy of a drug may be correlated with the enantiomer, if any, is bound to the receptor. For the case of binding affinity of the drug for diseased tissue; more effica more than one enantiomer binding to the receptor, it may be cious drugs tend to bind more strongly to proteins associated determined which is bound more strongly to the receptor. It is with a disease than less efficacious drugs do. Side effects of a important to determine which receptor(s) bind to each enan drug may be correlated with the ability of the drug to bind to tiomer of the chemical in order to identify any potential side healthy tissue. The choice of which drug to prescribe may be effects of a toxic enantiomer. Thalidomide, for example, is a based on the ability of the drug to bind strongly to the diseased chemical that was used to treat morning sickness until it was tissue (or to proteins associated with the diseased tissue) and discovered that a toxic enantiomer of the chemical was to bind weakly, or not at all, to healthy tissue (or to proteins responsible for birth defects. associated with health tissue). A cancer biopsy sample (i.e. 0163. In order to optimize the balance between the speed from a tumor), for example, may be lysed and arrayed on an of analysis versus the sensitivity of the XRF technique, it is analytical protein chip. The chip would then be exposed to a preferable that a sample of receptor, or chemical-receptor variety of chemotherapy drugs (or even cold radiopharma complex, be exposed to the X-ray excitation beam for a period ceutical Surrogates) and the relative binding affinities of the of time from about 100 milliseconds to about 600 seconds. To different drugs to the arrayed biopsy sample would guide the further optimize speed versus sensitivity, it is preferable that course of treatment. Side effects could be quantified and the X-ray excitation beam spends more time focused on a minimized by performing a similar assay using non-cancer pixel that contains receptor and/or receptor-chemical com ous tissue, and selecting the drug based on minimized drug plex than on a pixel that is substantially devoid of receptor or enzyme interactions. This method may also be used with drug receptor-chemical complex. This way, less time is wasted mixtures, which are sometimes referred to as "cocktails'. analyzing parts of a sample that have little useful information. 0.168. The invention may be used for participant stratifica 0164. An X-ray translucent barrier may be used with a tion in clinical trials of proposed drugs. Currently, participant receptor or receptor array in order to minimize evaporation stratification methods are based on DNA chips, where and evaporative cooling of receptors and/or chemicals. genomic profiles are correlated with the variation in partici 0.165 Another aspect of the present invention relates to pant response to chemicals (e.g. drug candidates). The corre use for personalized medicine. Personalized medicine is lation of genomic profiles with patient response is sometimes described in “Personalized Prescribing.” The Scientist, referred to as “pharmacogenomics'. Genomic profiles are 1512:10, Jun. 11, 2001, incorporated herein by reference. several steps removed from the proteomic profile of a partici Personalized medicine is important because it is expected to pant in a clinical trial of a drug; genetics and environmental US 2008/0220441 A1 Sep. 11, 2008 69 factors affect which proteins are expressed. Drugs regulate 0173 Another aspect of the invention relates to its use in protein behavior, and so the protein make-up of a particular measuring post-translational modification of proteins. Such participant and how those proteins interact with the drug(s) in as the phosphorylation or dephosphorylation of one or more a course of clinical trials will provide the best information for proteins. Phosphorylation and desphosphorylation reactions participant stratification. Protein chips have become inexpen are described by K. Martin et al. in “Quantitative Analysis Of sive and commercially available. Protein Phosphorylation Status And Protein Kinase Activity 0169. Regarding the use of the invention for participant On Microarrays. Using A Novel Fluorescent Phosphorylation stratification in a clinical trial of a drug such as an anti-cancer Sensor Dye.” Proteomics, vol. 3, pp. 1244-1255 (2003). This drug, a protein array on a protein chip may be exposed to paper describes the need for radioactive labeling and fluores protein extracts from a cancer patient, as described above. cent tagging; however, both radioactive labeling and fluores Protein extracts of the tumor and of healthy tissue would be cent tagging are unnecessary in view of the present invention, taken from the patient. After exposing the chip to the extracts, which can measure the amount of phosphorus directly in an a baseline XRF baseline spectrum would be obtained. Solu untagged protein using XRF. tions of each drug being tested in the trial would then be 0.174. An example of the use of the invention for measur contacted with the protein chip having the bound proteins. ing post-translational modifications may include establishing The binding affinity of each drug would then be measured a baseline X-ray fluorescence signal for a heavy element (i.e. according to the invention, which involves measuring the an element having anatomic number of nine or greater). Such XRF signals of heavy elements present in the drug-receptor as phosphorus, in a portion of a protein. The portion of protein complex, Subtracting out the baseline from this measurement, is then exposed to reaction conditions such as those described and then comparing the signals to see which drug exhibits a by K. Martin et al. in “Quantitative Analysis Of Protein Phos more selective binding to the tumor versus the healthy tissue phorylation Status And Protein Kinase Activity On Microar and/or which drug binds more strongly to the tumor. This rays. Using A Novel Fluorescent Phosphorylation Sensor information may then be correlated to the efficacy, toxicity, Dye.” Proteomics, Vol. 3, pp. 1244-1255, (2003), which alter and side effects of the drugs as measured in the clinical trials. the amount of phosphorus in the protein. The X-ray fluores The importance of clinical trial stratification is that if a drug cence signal due to the element would then be remeasured can be shown to only have unacceptable side effects for using XRF. Subtracting the baseline X-ray fluorescence signal people with specific genomic and/or proteomic profiles (i.e. a from the remeasured X-ray fluorescence signal provides a net strata), the drug may be approved for other strata for which X-ray fluorescence signal that may be correlated with the the drug has acceptable side effects. This process may allow amount of the element in the protein, which provides an drugs that would otherwise be rejected by the Food and Drug estimate of the extent of phosphorylation of the protein. Administration or other regulatory agencies to be accepted (0175. The following EXAMPLES provide an illustration for a more limited use, thereby allowing drug candidates to be of various aspects of this invention. used that would otherwise be rejected. 0170 Another aspect of the invention relates to drug Example 1 manufacturing. The drug manufacturing process is lengthy, 0176 Binding of ziprasidone to protein receptors. A pro typically including a period of time where a new drug is tein array may be prepared as described in G. MacBeath and discovered, another period of time where the drug is devel S. L. Schreiber, “Printing Proteins. As Microarrays For High oped, more time where the drug is tested with animals and Throughput Function Determination. Science, vol. 289, pp. then humans, and more time where the drug is synthesized on 1760-1763, (2000). This protein array may be exposed to a a larger and larger scale. Discovery involves determining Solution of Ziprasidone, which is the active ingredient in the which chemicals are likely to be effective drugs, and is often drug GeodonTM. Ziprasidone has a molecular formula of conducted by measuring the interaction between a chemical CHCINOS and the structure shown below. and a receptor (sometimes referred to in the art as a "drug gable target”). Development involves in vitro testing to esti mate the likely side effects and pharmacokinetics of a chemi cal. Animal testing is used to determine whether the drug is safe in animals, and are sometimes used to determine whether a drug is effective in animals. If the drug is deemed suffi N N ciently safe in animals, it may be administered to human Volunteers in clinical trials to determine human safety and efficacy. If a drug is deemed safe and effective in human k- a Volunteers, it may be mass-produced for use by physicians and patients. All of these steps are necessary. 0171 The invention may be used to estimate the efficacy Ziprasidone of a chemical (analog, drug). Measuring the affinity of one or more chemicals for a druggable target fulfills the discovery 0177. The elements chlorine and sulfur may each be step. detected by X-ray fluorescence. After the array is exposed to 0172. The invention may be used to estimate side effects the Ziprasidone-containing solution, an EDAX Eagle Micro and/or pharmacokinetics by measuring the binding selectiv probe X-ray fluorescence microscope, for example, could be ity of one or more chemicals for a druggable target versus used to determine the receptor proteins that bind to the other proteins that may be associated with side effects or Ziprasidone. The amount of Ziprasidone that is associated pharmacokinetics. Animal studies and human studies may with each receptor may be quantified by X-ray fluorescence. then be performed, followed by mass production of the drug 0.178 None of the proteins of the array are expected to using chemical synthesis or biological synthesis. contain the element chlorine, so the chlorine X-ray fluores US 2008/0220441 A1 Sep. 11, 2008 70 cence baseline may be assumed to be Zero (although the quantified and related to the binding of DNA from the solu chlorine x-ray fluorescence baseline could be measured). At tion to various receptors of the array. least Some of the proteins are expected to contain the element 0184. This DNA receptor array used with the EXAMPLE Sulfur (from Sulfur containing amino acids such as cysteine may be replaced with an array that includes other molecules, and methionine). Before exposing the array proteins to Ziprasidone, a baseline X-ray fluorescence signal for Sulfur such as RNA and peptides, to examine the binding of DNA may be obtained, and after exposure to the Ziprasidone, the from a solution to these other receptors. RNA may also be X-ray fluorescence signal due to Sulfur would be measured used as a probe molecule. again. The difference in the sulfur signals would be used to determine whether any receptor-Ziprasidone complex Example 4 formed, and measuring the amount of any Such complex that formed. 0185. Binding of drugs to protein receptors. A protein array may be prepared as described in Kukar et al., “Protein Example 2 Microarrays to Detect Protein-Protein Interactions Using Red (0179 Binding of ziprasidone to DNA receptors. A DNA and Green Fluorescent Proteins.” Analytical Biochemistry, array such as an Affymetrix GeneChipTM may be exposed to vol.306, pp. 50-54 (2002). This protein array may be exposed a solution that contains Ziprasidone, as described in to a solution of olanzapine (the active ingredient in EXAMPLE 1. After the array is exposed to the ziprasidone ZyprexaR) and aripiprazole (the active ingredient in containing solution, an EDAX Eagle Microprobe X-ray fluo AbilifyTM). Olanzapine has the chemical formula rescence microscope, for example, could be used to deter CHNS, and aripiprazole has the chemical formula mine the locations of those receptor DNA that bind to the C23H,ClNO. These molecules have the chemical struc Ziprasidone. The amount of Ziprasidone that is associated tures shown below. with each receptor may be quantified by X-ray fluorescence. 0180. None of the DNA receptors of the array are expected to contain the elements chlorine or sulfur, so the chlorine Olanzapine: X-ray fluorescence baseline and the sulfur X-ray fluorescence baseline may be assumed to be zero. After exposure to the Ziprasidone-containing Solution, the X-ray fluorescence sig nal due to sulfur and/or chlorine would be measured. The measured X-ray fluorescence signal(s) may be used to deter N mine whether any DNA-ziprasidone complex formed, and measuring the amount of any such complex that formed. 0181. The DNA receptors of the array may then be ana OC-( ) lyzed to identify which of the DNA receptor(s) bind to the I S CH ziprasidone and which fail to bind. With this information, H which is provided by this EXAMPLE, factors that affect Aripiprazole: binding may be determined. Example 3 0182 Binding of DNA receptors to DNA probe mol K- N N-CHCHCHCHO N O ecules. A DNA array such as an Affymetrix GeneChipTM may be exposed to a solution of DNA molecules that may or may not be complementary to the DNA on the array. If the DNA in 0186 Olanzapine may be detected and quantified by the solution is not complementary to any of the DNA on the array, X-ray fluorescence of its Sulfur atom and aripiprazole may be then no binding is expected to occur. If the DNA in solution detected and quantified by the X-ray fluorescence of its chlo were complementary to any of the DNA on the array, then rine atoms. some binding would be expected to occur. DNA molecules 0187. After the array is exposed to the solution that con include the element phosphorus that is detectable using X-ray tains a mixture of aripiprazole and olanzapine, the array may fluorescence of the phosphorus atoms. After the array is be analyzed using an EDAX Eagle Microprobe X-ray fluores exposed to the solution of DNA, the array may be analyzed cence microscope. The protein receptors that bind to olanza using an EDAX Eagle Microprobe X-ray fluorescence micro pine may be identified by the sulfur X-rays. The amount of scope. The DNA receptors of the array that bind to the added olanzapine that is associated with each receptor may be quan DNA from the DNA-containing solution may be identified by tified by X-ray fluorescence. The protein receptors that bind to the phosphorus x-rays, and the amount of added DNA that is aripiprazole may be identified by the chlorine X-rays. The associated with each receptor may be quantified by the X-ray amount of aripiprazole that is associated with each receptor fluorescence signal. may be quantified by X-ray fluorescence. 0183 Preferably, a baseline x-ray fluorescence signal for 0188 Preferably, a baseline x-ray fluorescence signal for each portion of DNA receptor would be obtained before chlorine and one for sulfur are measured for each receptor exposing the receptor array to the DNA containing solution to before exposing the receptors to the Solution. After contacting determine the phosphorus content of the DNA receptors of the array with the solution, the sulfur and chlorine content of the array. After exposing the array to the DNA solution, the each receptor would be measured again. The difference in the difference in the phosphorus X-ray fluorescence signals after measured Sulfur and chlorine X-ray fluorescence signal after contact and before contact with the DNA solution may be contact and before contact with the solution of aripiprazole US 2008/0220441 A1 Sep. 11, 2008

and olanzapine solution may be quantified and related to the as described, for example, in Kukar et al., “Protein Microar binding of aripiprazole and olanzapine to receptors in the rays to Detect Protein-Protein Interactions. Using Red and array. Green Fluorescent Proteins.” Analytical Biochemistry, vol. 306, pp. 50-54 (2002). Example 5 0.195. This protein array would be exposed to a solution of a mixture of olanzapine (C2HNS) and aripiprazole 0189 Binding of drugs to protein receptors. A protein (CH2Cl2.N.O.). Olanzapine may be detected and quanti array may be prepared as described in Kukar et al., “Protein fied by the X-ray fluorescence of its Sulfur atom, and aripipra Microarrays to Detect Protein-Protein Interactions Using Red Zole may be detected and quantified by the X-ray fluorescence and Green Fluorescent Proteins.” Analytical Biochemistry, of its chlorine atoms. vol.306, pp. 50-54 (2002). This protein array may be exposed 0196. After the array is exposed to the solution, the array to a solution that contains a mixture olanzapine (the active would be analyzed using an EDAX Eagle Microprobe X-ray ingredient in ZyprexaR) and acetylsalicylic acid (the active fluorescence microscope. The receptor proteins that bind to ingredient in aspirin). Olanzapine has the chemical formula olanzapine may be identified by their sulfur X-rays. The CHNS, and acetylsalicylic acid has the chemical for amount of olanzapine that is associated with each receptor mula CHO. Olanzapine may be detected and quantified by spot may be quantified by X-ray fluorescence. The receptor the X-ray fluorescence of its Sulfur atom. Acetylsalicylic acid, proteins that bind to aripiprazole may be identified by the however is more difficult to both to detect and differentiate chlorine X-rays. The amount of aripiprazole that is associated using X-ray fluorescence because it only contains carbon, with each spot may be quantified by X-ray fluorescence. oxygen and hydrogen, the X-ray fluorescence signals of which 0.197 Preferably, the a baseline X-ray fluorescence signal are overwhelmed by the corresponding signals in the protein for each receptor protein of the array is obtained before expo receptors. Sure to the Solution. After contacting the array with the solu 0190. After the array is exposed to the solution, the array tion, the Sulfur and chlorine content of each protein receptor may be analyzed using an EDAX Eagle Microprobe X-ray spot may be measured again. The difference in the Sulfur and fluorescence microscope. The protein receptors that bind to chlorine after contact and before contact with the solution olanzapine in the presence of acetylsalicylic acid may be may be quantified and related to the binding of aripiprazole identified by the net X-ray fluorescence signal from sulfur. and olanzapine to the receptors in the array. The amount of olanzapine that is associated with each recep 0198 Antherapeutic index for this patient for olanzapine tor may be quantified by X-ray fluorescence. and one for aripiprazole may be estimated using the X-ray 0191 Preferably, a baseline X-ray fluorescence measure fluorescence data. These estimated indices may be used to ment for the protein receptors of the array would be obtained guide the choice of drug to be administered. before exposure to the Solution containing acetylsalicylic acid and olanzapine. This analysis may be used to determine Example 7 the sulfur content of the protein spots on the array. After contacting the array with the solution, the Sulfur content of 0199 Patient Stratification. A series of protein arrays may each protein spot may be measured again. The difference in be prepared as described in Kukaret al., “Protein Microarrays the sulfur after contact and before contact with acetylsalicylic to Detect Protein-Protein Interactions. Using Red and Green acid and olanzapine solution may be quantified and related to Fluorescent Proteins.” Analytical Biochemistry, vol. 306, pp. the binding of olanzapine to various protein receptors in the 50-54 (2002). The protein arrays would be prepared using array when acetylsalicylic acid is present. samples from participants in clinical trials of pharmaceutical 0.192 For comparison, the procedure described above for compounds and/or formulations. This is an EXAMPLE for a this EXAMPLE may be repeated using a solution that study for determining the safety and/or efficacy of olanzap includes olanzapine without acetylsalicylic acid in order to 1C. determine whether the presence of acetylsalicylic acid has 0200. The protein arrays described above would be any effect on the binding affinity and binding selectivity of exposed to a solution that includes olanzapine (C7HNS). olanzapine to the protein receptors. After contacting the array Olanzapine may be detected and quantified by the X-ray fluo with the Solution containing olanzapine (without acetylsali rescence of its Sulfur atom. cylic acid), the Sulfur content of each protein spot may be 0201 After the array is exposed to the solution, the array measured again. The difference in the Sulfur after contact and may be analyzed using an EDAX Eagle Microprobe X-ray before contact with olanzapine solution may be quantified fluorescence microscope. The protein receptors that bind to and related to the binding of olanzapine to various spots in the olanzapine may be identified by the X-ray fluorescence signal array when acetylsalicylic acid is not present. The binding due to Sulfur. The amount ofolanzapine that is associated with information may be compared to the binding of olanzapine to each protein receptor spot may be quantified by X-ray fluo various spots in the array when acetylsalicylic acid is present. CSCCC. (0193 This EXAMPLE illustrates a particularly important 0202 Preferably, a baseline X-ray fluorescence signal aspect of the present invention, which relates to estimating the would be obtained for each receptor before exposure to the therapeutic index of a chemical (in this case, olanzapine) and solution. This analysis may be used to determine the sulfur comparing it to an estimated therapeutic index of a "cocktail” content of the protein spots on the array. After contacting the i.e. a mixture of two or more chemicals. array with the solution, the sulfur content of each protein spot may be measured again. The difference in the Sulfur content Example 6 after contact and before contact with olanzapine Solution may be quantified and related to the binding of olanzapine to 0194 Personalized Medicine. A question arises relating to various protein receptors in the array. which antipsychotic drug, olanzapine oraripiprazole, should 0203 The binding of olanzapine to various proteins or be prescribed for a patient. A protein array would be prepared classes of proteins may be then correlated with the results of US 2008/0220441 A1 Sep. 11, 2008 72 the clinical trial, in order to correlate protein-olanzapine bind estimating the affinity of the chemical for the receptor by ing characteristics with safety and/or efficacy of various for dividing the net X-ray fluorescence signal by the amount mulations of olanzapine-based drugs. of receptor in the portion of the receptor to obtain a 0204. It is preferable to use protein arrays rather than DNA quotient of the chemical to the receptor. arrays for patient stratification, because proteins are believed 2. The method of claim 1, wherein the receptor-chemical to control cell functions. However, this method may also be complex is deposited on a Substrate having a thickness of less used with DNA arrays, tissue arrays, cellular arrays, and the than 500 microns. like. 0205. In summary, the present invention provides a 3. The method of claim 1, wherein the receptor-protein method for measuring binding selectivities between chemi complex is deposited on a Substrate having a thickness of cals and receptors. The invention provides significant advan between twenty (20) nanometers and twenty-five (25) tages over known methods for measuring binding selectivity. microns. Known methods often require either radioactive chemicals, or 4. The method of claim 1, wherein the receptor-chemical chemicals that include a covalently attached label that fluo complex is deposited on a Substrate comprising at least 10% resces upon exposure to ultraviolet excitation radiation. Since of at least one of the following elements: beryllium, carbon, the invention does not require radioactive or chemically silicon, aluminum, iron, cobalt, and gold. tagged materials, the problems dealing with the handling of 5. The method of claim 1, wherein the substrate is a focus radioactive materials and the disposal of radioactively con ing chip. taminated waste are avoided. Importantly, since the use of artificially tagged materials is not required, there can be no 6. The method of claim 5, wherein the focusing chip is interference from the tag in the evaluation of the binding substantially free of at least one of the elements selected from affinity of the corresponding desired untagged material. Fur the group of Sulfur, fluorine, phosphorus, chlorine, bromine, ther, in contrast to methods that require tags, the method of the iron, Zinc, magnesium, calcium, titanium, Scandium, and present invention can be used to evaluate the binding affinity platinum. of materials that do not fluoresce while exposed to ultraviolet 7. The method of claim 5, wherein the focusing chip has radiation. It should be understood that although tagged mate one or more hydrophilic regions, wherein at least one of the rials are not required, they could also be used and this aspect hydrophilic regions has an area of between 75 square picom of the invention offers a distinct advantage in that the inven eters and 3.6 square microns. tion can provide a direct comparison of binding affinity of the 8. The method of claim 1, wherein the cross section of the untagged chemical with that of the corresponding tagged excitation X-ray beam is between 25% and 250% of the area Surrogate. This comparison could validate or invalidate the of the receptor-chemical complex. assumption that a particular untagged chemical and its tagged 9. The method of claim 1, wherein the protein-receptor Surrogate have the same binding affinity to a particular Sub complex is exposed to a solution prior to measurement, the Strate. solution comprising a buffer which is substantially free of at 0206. The foregoing description of the invention has been least one chemical element having an atomic number of presented for purposes of illustration and description and is greater than four, where that chemical element is present in not intended to be exhaustive or to limit the invention to the the chemical. precise form disclosed, and obviously many modifications 10. The method of claim 1, wherein the receptor-chemical and variations are possible in light of the above teaching. complex is exposed to a solution prior to measurement, the 0207. The embodiment(s) were chosen and described in solution comprising a buffer, the buffer being substantially order to best explain the principles of the invention and its free of at least one of the chemicals or functional groups practical application to thereby enable others skilled in the art selected from the group of dimethylsulfoxide, thiols, sulfate to best utilize the invention in various embodiments and with anion, Sulfonate anions, chloride anion, bromide anion, fluo various modifications as are Suited to the particular use con ride anion, iodide anion, perchlorate anion, phosphate anion, templated. It is intended that the scope of the invention be and phosphonate anions. defined by the claims appended hereto. 11. The method of claim 1, wherein the receptor-chemical What is claimed is: complex is exposed to a solution prior to measurement, the 1. A method for estimating the binding affinity of a chemi Solution comprising a buffer, and the buffer comprises one or cal having at least one heavy element to a receptor, compris more of the chemicals or functional groups selected from the ing: group of amine, imine, nitrate anion, nitrite anion, ammo establishing a baseline X-ray fluorescence signal for a nium cation, and iminium cation. heavy element in the first receptor, the heavy element 12. The method of claim 1, wherein the receptor-chemical being presentina chemical to be tested for binding to the complex is purified using gel filtration chromatography or receptors; dialysis prior to analysis. exposing the receptor to the chemical and allowing the 13. The method of claim 12, wherein the receptor-chemical chemical to bind to them to form a chemical-receptor complex is purified using a chromatographic process which complex: includes a vacuum or centrifugation step. measuring the X-ray fluorescence signals due to the heavy 14. The method of claim 1, wherein the receptor-chemical element in the chemical-receptor complex; complex is exposed to a solution prior to measurement, the Subtracting the baseline X-ray fluorescence signal of the Solution comprising a matrix modifier. receptor from the measured X-ray fluorescence signal of 15. The method of claim 1, wherein the X-ray fluorescence the of the chemical-receptor complex to obtain a net is measured using a chromium, palladium or silver X-ray X-ray fluorescence signal; SOUC. US 2008/0220441 A1 Sep. 11, 2008

16. The method of claim 1, wherein the X-ray fluorescence nisolone, flurandrenolide, flurazepam, flurbiprofen, fluta is measured using an X-ray source having a K-alpha or L-al mide, fluticaSone, fluvastatin, fluvoxamine, fomivirsen, pha line at or above about 2.838 KeV and less than about fondaparinux, foSamprenavir, foScarnet, fosfomycin 9.441 KeV. tromethamine, fosinopril, froVatriptan, fulvestrant, furo 17. The method of claim 1, wherein the chemical com semide, gadobenate, gadodiamide, gadopentetate, gadoteri prises at least one of the chemicals selected from the list of dol, gadoversetamide, gallium citrate, gallium salts, ganire abarelix, abciximab, acamprosate, acetazolamide, aceto lix, gatifloxacin, gefitinib, gemcitabine, gemifloxacin, hexamide, acetophenazine, acetrizoate, acetylcysteine, ade glimepiride, glipizide, glucagon, glyburide, grepafloxacin, fovir dipivoxil, alatrofloxacin, albendazole, alclometaSone, griseofulvin, guanabenz, guanfacine, halazepam, halobeta alendronate, almotriptan, alprazolam, ambenonium, amifos Sol, halofantrine, haloperidol, haloprogin, halothane, hep tine, amiloride, amiodarone, amlodipine, amlodipine, amo arin, hexachlorophene, hydrochlorothiazide, hydrocortisone, diaquine, amoxapine, amoxicillin, amplicillin, amprenavir, hydroflumethiazide, hydroxocobalamin, hydroxychloro anagrelide, anakinra, apraclonidine, aprepitant, ardeparin, quine, hydroxyzine, ibandronate, ibutilide, idoxuridine, ifos argatroban, articaine, atorvastatin, atovaquone, auranofin, famide, imipenem, indapamide, indium and its salts, indium azathioprine, azelastine, azlocillin, aztreonam, bacampicil oxyquinoline, indium pentetate, indium, indocyanine green, lin, bacitracin, baclofen, beclomethasone, bendroflumethiaz indomethacin, iobenguane, iocetamic acid, iodamide, iodipa ide, benzthiazide, betamethasone, bicalutamide, bismuth mide, iodixanol, iodohippurate, iofetamine, iohexyl, iopami Subsalicylate, bleomycin, bosentan, bretylium, brimonidine, dol, iopanoic acid, iopromide, iothalamate, iothalamate, brinzolamide, bromfenac, bromocriptine, bromodiphenhy iotrolan, ioVersol, ioxaglate, ioXilan, ipodate, isoflurane, isof dramine, brompheniramine, buclizine, bumetanide, bupro luorophate, itraconazole, ketamine, ketoconazole, ketotifen, pion, buSulfan, butalbital, butoconazole, capecitabine, lamivudine, lamotrigine, lanSoprazole, leflunomide, levami capreomycin, captopril, carbenicillin, carbenicillin indanyl. sole, levocabastine, levofloxacin, levothyroxine, lincomycin, carbinoxamine, carboplatin, carmustine, carphenazine, car lindane, lineZolid, liothyronine, lodoxamide, lomefloxacin, profen, cefaclor, cefadroxil, cefamandole, cefazolin, cefdinir, lomustine, loperamide, loracarbef, loratadine, lorazepam, cefditoren, cefepime, cefixime, cefimenoXime, cefimetazole, losartan, loteprednol, loxapine, mafenide, magnesium salts, cefonicid, cefoperaZone, ceforanide, cefotaxime, cefotetan, malathion, mangafodipir, manganese salts, mazindol, cefotiam, cefoxitin, cefpiramide, cefpodoxime proxetil, cef mechlorethamine, meclizine, meclocycline, meclofenamate, prozil, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, mefloquine, meloxicam, melphalan, mercaptopurine, mero cefuroxime, cefuroxime axetil, celecoxib, cephalexin, cepha penem, mersalyl, mesoridazine, methazolamide, methdila loglycin, cephalothin, cephapirin, cephradine, cerivastatin, Zine, methicillin, methimazole, methixene, methotrimepra cetirizine, cetrorelix, cevimeline, chlophedianol, chloram Zine, methoxyflurane, methyclothiazide, metoclopramide, bucil, chloramphenicol, chlordiazepoxide, chlorhexidine, metolaZone, metrizamide, mezlocillin, micafungin, micona chlormeZanone, chloroprocaine, chloroquine, chlorothiaz Zole, midazolam, mitotane, modafinil, mometaSone, mon ide, chlorotrianisene, chloroxine, chlorphenesin, chlorphe telukast, moxalactam, moxifloxacin, nafcillin, naratriptan, niramine, chlorphentermine, chlorpromazine, chlorpropam nefazodone, nelfinavir, niclosamide, nilutamide, nitaZOX ide, chlorprothixene, chlortetracycline, chlorthalidone, anide, nizatidine, nofetumomab, norfloxacin, octreotide, chlorZoxazone, chromium picolinate, chromium salts, cilas ofloxacin, omeprazole, oxacillin, oxaliplatin, oxazepam, oxi tatin, cimetidine, cinacalcet, ciprofloxacin, cisapride, cispl conazole, oxytocin, pamidronate, pantoprazole, parametha atin, citalopram, cladribine, clemastine, clindamycin, clinda Sone, paroxetine, pegaptainib, penicillamine, penicilling ben mycin, clindamycin, clioquinol, clobetasol, clocortolone, Zathine, penicillin V, pentetate, pentosan polysulfate, clofarabine, clofazimine, clofibrate, clomiphene, clomi perflexane, perflubron, perfluoropolymethylisopropyl ether, pramine, clonazepam, clonidine, clopidogrel, cloraZepate, perflutren, pergolide, permethrin, perphenazine, phenoxy clotrimazole, cloxacillin, clozapine, colestipol, cyclophos benzamine, pimecrolimus, pimozide, pioglitaZone, piperac phamide, cyclothiazide, cysteamine, cysteine, dalfopristin, etazine, piperacillin, pipobroman, piroxicam, polythiazide, dapsone, delavirdine, demeclocycline, desflurane, deslorata porfimer, potassium salts, povidone-iodine, pramipexole, dine, desmopressin, dexamethasone, dexamethasone, dex pramlintide, prazepam, prednisolone, probenecid, probucol, amethasone, dexbrompheniramine, dexchlorpheniramine, prochlorperazine, proguanil, promazine, promethazine, pro diatrizoate, diazepam, diazoxide, dichlorphenamide, piomazine, propyliodone, propylthiouracil, pyrimethamine, diclofenac, dicloxacillin, diethylstilbestrol, diflorasone, pyrithione Zinc, quaZepam, quetiapine, quinethaZone, quinu diflunisal, diltiazem, dimenhydrinate, dimercaprol, dimethyl pristin, rabeprazole, raloxifene, ranitidine, ranitidine bismuth sulfoxide, dimyristoyl, disulfiram, dofetilide, dorzolamide, citrate, riluzole, risedronate, risperidone, ritonavir, rofecoxib, droperidol, dulloxetine, dutasteride, echothiophate, econa rose bengal, rosiglitaZone, rosuvastatin, rubidium salts, Zole, efavirenz, eflornithine, eletriptan, emitricitabine, enflu Samarium lexidronam, selenium sulfide, selenite salts, sel rane, enoxacin, eprosartan, eptifibatide, ertapenem, escitalo enate salts, selenomethionine, Sertaconazole, Sertraline, pram, esmolol, esomeprazole, estazolam, estramustine, sevoflurane, Sibutramine, sildenafil, silver Sulfadiazine, sim eSZopiclone, ethacrynate, ethacrynic acid, ethchlorVynol, ethicone-cellulose, sodium fluoride, Sodium iodide, Sotalol, ethiodized oil, ethionamide, ethopropazine, ethoXZolamide, sparfloxacin, spirapril, spironolactone, strontium chloride, etidronate, etoposide, evans blue, eZetimibe, famotidine, Succimer, Sucralfate, Sufentanil, Sulconazole, Sulfacetamide, felodipine, fenofibrate, fenoldopam, flecamide, floxuridine, Sulfacytine, Sulfadiazine, Sulfadoxine, Sulfamerazine, Sul fluconazole, flucytosine, fludarabine, fludeoxyglucose, fameter, Sulfamethizole, Sulfamethoxazole, Sulfanilamide, fludrocortisone, flumazenil, flumethasone, flunisolide, fluo Sulfaphenazole, Sulfasalazine, Sulfinpyrazone, Sulfisoxazole, cinolone acetonide, fluocinonide, fluorometholone, fluo Sulfisoxazole acetyl, Sulfoxone, Sulfur, Sulindac, Sumatriptan, rometholone, fluorouracil, fluoxetine, fluoxymesterone, Sumatriptan, Suprofen, tamsulosin, tazarotene, taZobactam, fluiphenazine, fluiphenazine enanthate, fluiphenazine, flupred temazepam, teniposide, tenofovir disoproxil, terconazole, US 2008/0220441 A1 Sep. 11, 2008 74 thallous chloride, thiabendazole, thiamine, thiamylal, thieth nase; 3 Alpha-Hydroxysteroid Dehydrogenase Type 3: ylperazine, thioguanine, thiopental, thioridazine, thiotepa, 3-Alpha-Hydroxysteroid/Dihydrodiol Dehydrogease; 3-Car thiothixene, tiagabine, ticarcillin, ticlopidine, tiludronate, boxy-Cis.Cis-Muconate Cycloisomerase: 3-Dehydroquinate timolol, tinidazole, tinzaparin, tioconazole, tiopronin, tiotro Dehydratase; 3-Dehydroquinate Dehydratase Arod; 3-Dehy pium, tirofiban, tizanidine, tolaZamide, tolbutamide, topira droquinate Synthase; 3-Deoxy-D-Arabino-Heptulosonate-7- mate, toremifene, torsemide, travoprost, traZodone, triamci Phosphatase; 3-Deoxy-Manno-Octulosonate Cytidylyltrans nolone, triamcinolone acetonide, triamcinolone diacetate, fer; 3-Hydroxy-3-Methylglutaryl-CoaSynthase: 3-Hydroxy triamcinolone hexacetonide, triazolam, trichlormethiazide, 3-Methylglutaryl-Coenzyme A Reductase; 3-Hydroxyacyl triclofos, triclosan, trifluoperazine, triflupromazine, trifluri Coa Dehydrogenase; 3-Hydroxyacyl-Coa Dehydrogenase dine, trimeprazine, trimethaphan, troglitaZone, trovafloxacin, Type 1 I: 3-hydroxyisobutyrate dehydrogenase, mitochon tyropanoate, uracil mustard, Valdecoxib, valrubicin, Vanco drial precursor; 3-Isopropylmalate Dehydrogenase; 3-Ke mycin, Vardenafil. Voriconazole, Zafirlukast, Ziconotide, toacetyl-Coa Thiolase; 3-Keto-L-Gulonate 6-Phosphate Zileuton, Ziprasidone, and Zoledronic acid. Decarboxylase; 3-keto-steroid reductase: 3-Mercaptopyru 18. The method of claim 1, wherein the receptor comprises Vate Sulfurtransferase: 3-Methyl-2-Oxobutanoate at least one of the receptors selected from the list of 1,3,4,6- Hydroxymethyltra; 3-Methyl-2-Oxobutanoate Hydroxym Tetrachloro-1,4-Cyclohexadiene H; 1,3,6,8-Tetrahydrox ethyltransfe; 3-Methyladenine DNA Glycosylase; 3-Methy ynaphthalene Reductase; 1,3-1,4-Beta-Glucanase; 1,4-Alpha laspartate Ammonia-Lyase, 3-oxo-5-alpha-steroid 4-dehy Maltotetrahydrolase; 1,4-Alpha-D-Glucan Glucanohydro drogenase 2: 3-Oxoacyl-, 3-Oxoacyl-Acyl-Carrier Protein lase; 1,4-Beta-D-Glucan Cellobiohydrolase Cel7; 1,4-Beta Reductase: 3-Oxoacyl-Acyl-Carrier Protein Synthas; D-Glucan Cellobiohydrolase I: 1,4-dihydropyridine Recep 3-Oxoacyl-Acyl-Carrier-Protein Synthas; 3-oxoacyl-acyl tor on alpha1 subunit of L-type Voltage sensitive Ca2+ carrier-protein synthase I: 3-oxoacyl-acyl-carrier-protein channels; 10 Kda Chaperonin; 10-Formyltetrahydrofolate synthase II: 3-oxoacyl-acyl-carrier-protein synthase III; Dehydrogenase; 11-cis retinol dehydrorgenase; 12-OXophy 3-Phosphoglycerate Kinase; 3-Phosphoinositide Dependent todienoate Reductase; 12-Oxophytodienoate Reductase 1: Protein Kin; 3-Phosphoinositide Dependent Protein Kinase-; 12-Oxophytodienoate-10, 11-Reductase; 14-3-3-Like Pro 3-Phosphoshikimate 1-Carboxyvinyltransferase: 3-Phytase tein C: 15-hydroxyprostaglandin dehydrogenase NAD+: A; 47 Kda Membrane Antigen: 4-Alpha-Glucanotransferase: 17-Beta-Hydroxysteroid Dehydrogenase; 17-Beta-Hydrox 4-Amino-4-Deoxychorismate Lyase: 4-Aminobutyrate Ami ysteroid Dehydrogenase 4; 17 Kd Fetal Brain Protein; notransferase: 4-Chlorobenzoyl Coa Ligase: 4-Chloroben 19-Mer Peptide Fragment Of Rhodopsin: 1-Aminocyclopro Zoyl Coenzyme A Dehalogenase: 4-Cresol Dehydrogenase pane-1-Carboxylate Deaminase: 1-Deoxy-D-Xylulose Hydroxylating Flavo: 4-Diphosphocytidyl-2-C-Methyl-D- 5-Phosphate Reductois; 1-Pyrroline-5-Carboxylate Dehy Erythrit: 4-Diphosphocytidyl-2-C-Methylerythritol Synt; drogenase; 1 SY6:H OKT3 Heavy Chain 1; 1SY6:L OKT3 4-Hydroxybenzoyl-Coa Thioesterase: 4-Hydroxyphe Light Chain 1: 2,2-Dialkylglycine Decarboxylase: 2,3-Bis nylpyruvate Dioxygenase, 4-Hydroxyphenylpyruvic Acid phosphoglycerate-Independent Phosphog: 2,3-Dihydroxy Dioxygenase: 4-Hydroxythreonine-4-Phosphate Dehydro benzoate-Amp Ligase; 2.3-Dihydroxybiphenyl Dioxyge genase; 4M5.3 Anti-Fluorescein Single Chain Antibody; nase, 2,3-Dihydroxybiphenyl-1,2-Dioxygenase; 2,4- 4-Oxalocrotonate Tautomerase: 4'-Phosphopantetheinyl Dienoyl-Coa Reductase; 2,5-Diketo-D-Gluconic Acid Transferase Sfp: 4-trimethylaminobutyraldehyde dehydroge Reductase: 23-Kda Polypeptide Of Photosystem II Oxygen-: nase; 5,10-Methenyltetrahydrofolate Synthetase; 5,10-Meth 23S Ribosomal; 23S Ribosomal RNA; 23S rRNA of 50S ylenetetrahydrofolate Dehydrogenase; 5,10-Methylenetet ribosomal subunit; 25-hydroxyvitamin D-1 alpha hydroxy rahydrofolate Reductase: 50S Ribosomal Protein L1P, 50S lase, mitochondrial; 2'-5'-Oligoadenylate Synthetase 1; 26S subunit of the 70S ribosome of bacteria: 5-alpha reductase 1: proteasome non-ATPase regulatory subunit 1, 2-amino-3- 5-Aminolaevulinic Acid Dehydratase: 5-aminolevulinate ketobutyrate coenzyme Aligase; 2-Amino-4-Hydroxy-6-Hy synthase: 5-Aminolevulinic Acid Dehydratase; 5'-AMP-acti droxymethyldihydropte: 2-amino-4-hydroxy-6-hydroxym vated protein kinase, beta-2 subunit; 5'-AMP-activated pro ethyldihydropteridine pyrophosphokinase; tein kinase, catalytic alpha-1 chain; 5'-D: 5'-Deoxy-5'-Meth 2-Aminoethylphosphonate-Pyruvate Aminotr; 2-C-Methyl ylthioadenosine Phosphorylas; 5-Enolpyruvylshikimate-3- D-Erythritol 2.4-Cyclodiphosphate: 2-C-Methyl-D-Erythri Phosphate Synthase; 5-Epi-Aristolochene Synthase: tol 4-Phosphate Cytidyl); 2C-Methyl-D-Erythritol-2,4-Cy 5'-Fluoro-5'-Deoxyadenosine Synthase; 5-HT1A Receptor; clodiphosphate: 2-Dehydro-3-Deoxyphosphooctonate 5-HT-1B Receptor; 5-HT1D Receptor; 5-HT2A Receptor; Aldolase: 2-Enoyl-Coa Hydratase: 2-Haloacid Dehaloge 5-HT-3 Receptor; 5HT4 receptor; 5-hydroxytryptamine 1E nase: 2-Isopropylmalate Synthase: 2-Keto-3-Deoxy Glucon receptor; 5-hydroxytryptamine 1F receptor; 5-hydrox ate Aldolase; 2-Keto-3-Deoxygluconate Kinase: 2-oxoglut ytryptamine 2C receptor; 5-hydroxytryptamine 7 receptor; arate dehydrogenase E1 component, mitochondrial 5-Methyltetrahydrofolate S-Homocysteine; 5-Methyltet precursor; 2-Pyrone Synthase; 3 beta-hydroxysteroid dehy rahydrofolate S-Homocysteine Meth: 5-Methyltetrahy drogenase/delta 5-; 3.2-Trans-Enoyl-Coa Isomerase, Mito dropteroyltriglutamate-: 5-Methyltetrahydropteroyltri chondrial: 3,4-Dihydroxy-2-Butanone 4-Phosphate Syn glutamate-Homo; 5'-Methylthioadenosine Phosphorylase; thase; 3',5'-Cyclic Nucleotide Phosphodiesterase 2A; 30S 5'-Nucleotidase; 5'-R: 6,7-Dimethyl-8-Ribityllumazine Syn ribosomal protein S12:30S ribosomal protein S4; 30S Ribo thase; 6-Deoxyerythronolide B Hydroxylase; 6-Hydroxym somal Protein S6:30S ribosomal protein S9; 32.1 Kda Protein ethyl-7,8-Dihydropterin Pyrophosph; 6-Oxocamphor In Adh3-Rcal Intergenic; 33 Kda Chaperonin; 3'-5' Exonu Hydrolase; 6-Phospho-Beta-D-Galactosidase; 6-Phospho clease Eri1; 36 Kda Soluble Lytic Transglycosylase; 367Aa Beta-Glucosidase; 6-Phosphofructo-2-Kinase/Fructose-2,6- Long Hypothetical Cytochrome P450; 385Aa Long Con Bisp; 6-Phosphofructo-2-Kinase/Fructose-2,6-Bipho: served Hypothetical Protein: 3-Alpha, 20-Beta-Hydroxys 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisph; 6-Phosphof teroid Dehydrogenase; 3-Alpha-Hydroxysteroid Dehydroge ructokinase; 6-Phosphogluconate Dehydrogenase; 6-Phos US 2008/0220441 A1 Sep. 11, 2008 phogluconolactonase; 6-Pyruvoyl Tetrahydropterin Syn ADP-Ribosylation Factor 6; ADP-Ribosylation Factor-Like thase; 7 Alpha-Hydroxysteroid Dehydrogenase; 7.8- 8; ADP-Ribosylation Factor-Like Protein 1; ADP-Ribosyla Diamino-Pelargonic Acid Aminotransferase; 7.8-Dihydro-6- tion Factor-Like Protein 3; ADP-Ribosylation Factor-Like Hydroxymethylpterin-Pyrophosp;70 Kilodalton Heat Shock Protein 5; ADP-Ribosyltransferase; Adrenodoxin; Adreno Protein: 70-Kda Soluble Lytic Transglycosylase; 7-dehydro doxin Reductase; Adsorption Protein P2: Aequorin; Aequorin cholesterol reductase; 8-Amino-7-Oxononanoate Synthase: 2: Aeromonas caviae: AFG3-like protein 1: AFG3-like pro 8-Oxoguanine DNA Glycosylase; 92 Kda Type IV Collage tein 2: Agglutinin; Agglutinin; Agglutinin Isolectin 3; Agglu nase; A chain, A/G-Specific Adenine Glycosylase; Aac; tinin Isolectin I/Agglutinin Isolect; Agglutinin Isolectin Vi; Aah2: Lch-Alpha-It: Abc Transporter, ATP Binding Protein; Agglutinin Isolectin Vi/Agglutinin Isolec.; Agmatinase; Acetate Kinase; Acetoacetyl-Coa Thiolase; Acetohydroxy Agmatine Iminohydrolase; Agrobacterium Timefaciens Dps; Acid Isomeroreductase; Acetohydroxy-Acid Synthase; Ahplaao; Aicar Transformylase-Imp Cyclohydrolase; Acetoin Reductase; Acetolactate Synthase, Catabolic; Aceto Alamethicin; Alanine aminotransferase; Alanine Dehydroge lactate Synthase, Mitochondrial; Acetyl Group: Acetyl Trans nase; Alanine Racemase; Alanine racemase, biosynthetic; ferase: Acetyl Xylan Esterase: Acetylcholine Binding Pro Alanine-Glyoxylate Aminotransferase; Alanine-glyoxylate tein: Acetylcholine-Binding Protein: Acetylcholinesterase: aminotransferase 2: Alanyl-tRNA synthetase; Alcohol Dehy Acetylcholinesterase: Acetylcholinesterase (AChE); Acetyl drogenase; Alcohol Dehydrogenase; Alcohol dehydrogenase cholinesterase precursor; Acetyl-Coa Acetyltransferase; NADP+: Alcohol dehydrogenase 6: Alcohol Dehydroge Acetyl-CoA Acetyltransferase (Mitochondrial); Acetyl-Coa nase Alpha Chain; Alcohol Dehydrogenase Beta Chain; Alco Carboxylase; Acetyl-CoA carboxylase 2: Acetyl-Coa Syn holdehydrogenase class II pichain precursor, Alcohol Dehy thetase: Acetyl-Coenzyme AAcetyltransferase 2: Acetyl-Co drogenase Class III Chi Chain; Alcohol dehydrogenase class enzyme A Carboxylase; Acetyl-Coenzyme A Synthetase 1: IV mu?sigma chain; Alcohol Dehydrogenase Class IV Sigma Acetyl-coenzyme A synthetase 2-like, mitochondrial; Chain; Alcohol Dehydrogenase E Chain; Alcohol Dehydro Acetyl-coenzyme A synthetase, cytoplasmic; Acetyl genase Gamma Chain; Alcohol Dehydrogenase, Class II; glutamate Kinase; Acidic Fibroblast Growth Factor; Acidic Alcohol Dehydrogenase, Class II; Alcohol Dehydrogenase, Lectin; Acireductone Dioxygenase; Aclacinomycin Methyl Iron-Containing; Alcohol Sulfotransferase; Aldehyde Dehy esterase; Aclacinomycin-10-Hydroxylase; Aconitase; Aconi drogenase; Aldehyde Dehydrogenase; Aldehyde dehydroge tate Hydratase; Aconitate Hydratase 2: Acriflavine Resis nase 1A3; Aldehyde dehydrogenase 3B1; Aldehyde dehydro tance Protein B; Actagardine; Actin; Actin Alpha 1: Actin genase 3B2; Aldehyde dehydrogenase family 7 member Al; Depolymerizing Factor; Actin, Alpha Skeletal Muscle; Actin Aldehyde dehydrogenase X, mitochondrial precursor; Alde Fragmin Kinase; Activated Cdc42 Kinase 1: Activator Of hyde Dehydrogenase, Cytosolic 1: Aldehyde dehydrogenase, Activin receptor; Activin Receptor Type II: Actva-Orf6 dimeric NADP-preferring; Aldehyde Dehydrogenase, Mito Monooxygenase; Acutohaemonly sin; Acyl Carrier Protein; chondrial Precur; Aldehyde dehydrogenase, mitochondrial Acyl Carrier Protein Phosphodiesterase: Acyl Carrier Protein precursor; Aldehyde Ferredoxin Oxidoreductase Protein C: Synthase; Acyl carrier protein, mitochondrial precursor, Aldehyde oxidase; Aldehyde Oxidoreductase; Aldehyde Acyl-Acyl-Carrier Protein Desaturase: Acyl-Acyl-Carrier Reductase; Aldo-Keto Reductase Family 1 Member C1; Protein-Udp-N-Acetylgl; Acylamino-Acid-Releasing Aldo-keto reductase family 1 member C2; Aldo-Keto Reduc Enzyme: Acyl-Coa Dehydrogenase; Acyl-CoA dehydroge tase Family 1 Member C3; Aldo-keto reductase family 1 nase family member 8: Acyl-Coa Dehydrogenase Family member C4; Aldolase; Aldolase Protein; Aldose 1-Epime Member 8, Mito. Acyl-Coa Dehydrogenase, Medium-Chain rase; Aldose Reductase; Alginate Lyase; Algal; Algo2; ALK Specifi, Acyl-CoA dehydrogenase, short-chain specific, tyrosine kinase receptor, Alkaline Phosphatase; Alkaline mitochondrial precursor; Acyl-Coa Hydrolase; Acyl-Coa Phosphatase: Alkyl Hydroperoxide Reductase Subunit F: Oxidase; Acyl-CoaThioesterase I: Acyl-Coa Thioesterase II; Allantoate Amidohydrolase; Allene Oxide Synthase-Lipoxy Acyl-Coenzyme A Binding Protein; acyl-coenzyme A: cho genase Protein; Alliin Lyase; Alpha Amylase; Alpha Glu lesterol acyltransferase; Acylphosphatase; Adam 33: Ada tathione S-Transferase: Alpha, Alpha-Trehalose-Phosphate malysin II: Adenine Glycosylase; Adenine Phosphoribosyl Synthase; Alpha-1 Catenin, Alpha1.2-Mannosidase; Alpha transferase; Adenine-N-6-DNA-Methyltransferase Taqi; 1.2-Mannosidase; Alpha-1,3-Mannosyl-Glycoprotein Beta Adenosine 2B receptor, Adenosine A1 receptor, Adenosine 1.2-N-; Alpha-1,4-Galactosyl Transferase: Alpha-1,4-Glu A3 receptor; Adenosine Deaminase; Adenosine Kinase; can-4-Glucanohydrolase; Alpha-1,4-N- Adenosylcobinamide Kinase; Adenosylhomocysteinase; Acetylhexosaminyltransferase Ext; Alpha-1A Adrenergic Adenosylmethionine-8-Amino-7-Oxononanoat, Adenosyl Receptor; Alpha1-Antitrypsin; Alpha-1-Antitrypsin, Alpha methionine-8-Amino-7-Oxononanoate Am; Adenylate 1B adrenergic receptor, Alpha-1D adrenergic receptor; Cyclase; Adenylate cyclase (cAMP); Adenylate Kinase; Ade Alpha-1-Purothionin; Alpha-2.3/8-Sialyltransferase: Alpha nylate Kinase 1: Adenylate Kinase Isoenzyme-3; Adenylo 2A Adrenergic Receptor; Alpha-2B adrenergic receptor; Succinate Synthetase; AdenyloSuccinate synthetase isozyme Alpha-2C adrenergic receptor; Alpha-2-Macroglobulin; 1: Adenylyl Cyclase; Adenylylsulfate Kinase; Adipocyte Alpha-2U-Globulin; Alpha-aminoadipic semialdehyde syn Lipid Binding Protein: Adipocyte Lipid-Binding Protein; thase, mitochondrial precursor, Alpha-Amylase; Alpha ADP Compounds Hydrolase Nude; ADP, ATP Carrier Protein Amylase I: Alpha-Amylase II; Alpha-Amylase Isozyme 1: Heart Isoform T1: ADPATP carrier protein, fibroblast iso Alpha-Amylase, Pancreatic; Alpha-Amylase, Salivary; form; ADPATP carrier protein, heart/skeletal muscle isoform AlphaChain (LH); Alpha-Conotoxin Gid: Alpha-D-Glucose T1:ADPATP carrier protein, liver isoform T2: ADP-Depen 1,6-Bisphosphate Phosphotran; Alpha-D-Glucuronidase; dent Glucokinase; ADP-L-Glycero-D-Mannoheptose 6-Epi Alpha-Galactosidase; Alpha-Galactosidase A.; Alpha-Glu merase; Adpr Pyrophosphatase; ADP-Ribose Pyrophos cosidase; Alpha-Glucosidase; Alpha-Glucuronidase; Alpha phatase; ADP-Ribosyl Cyclase; ADP-Ribosylation Factor 1: Ketoglutarate-Dependent Taurine Dioxyg: Alpha-L-Ara ADP-Ribosylation Factor 2; ADP-Ribosylation Factor 4: binofuranosidase; Alpha-L-Arabinofuranosidase B: Alpha US 2008/0220441 A1 Sep. 11, 2008 76

Lytic Protease; Alpha-Mannosidase II; Alpha-Momorcharin; ferase; Arylsulfatase; Arylsulfatase A: Arylsulfatase A: Alpha-Momorcharin Complexed With Adenine: Alpha-Mo Ascorbate Oxidase; Ascorbate Peroxidase; Asparagine Syn morcharin Complexed With Formycin; Alpha-N-Acetylga thetase; Asparagine Synthetase B; Asparaginyl-tRNA syn lactosaminidase; Alpha-N-acetylgalactosaminidase precur thetase; Aspartate 1-Decarboxylase; Aspartate 1-Decarboxy sor; Alpha-N-acetylglucosaminidase precursor; Alpha lase Precursor; Aspartate Aminotransferase; Aspartate Neurotoxin Tx12: Alpha-Tocopherol Transfer Protein; Aminotransferase; Aspartate aminotransferase, cytoplasmic; Alpha-Trehalose-Phosphate Synthase: Alpha-Trichosanthin Aspartate aminotransferase, mitochondrial; Aspartate Dehy Complexed With Adenine; Amic; Amicyanin; Amidase drogenase; Aspartate Receptor, Aspartate Transcarbamoy Operon; Amidophosphoribosyltransferase; Amidophospho lase; Aspartate-Semialdehyde Dehydrogenase; Aspartic Pro ribosyltransferase precursor; Amidophosphoribosyltrans tease Bla G. 2; Aspartic Proteinase; Aspartoacylase; Asparty1 ferase precursor; Amidotransferase Hish; Amiloride-sensi aminopeptidase; Asparty1/asparaginyl beta-hydroxylase; tive amine oxidase copper-containing precursor; Aspartyl-tRNA Synthetase: Aspergillopepsin; Assemblin; Amiloride-sensitive cation channel 1, neuronal; Amiloride Astacin: At5G 11950; ATP Phosphoribosyltransferase: ATP sensitive cation channel 2, neuronal; Amiloride-sensitive Sulfurylase; ATP Synthase; ATP synthase delta chain, mito Sodium channel alpha-Subunit; Amiloride-sensitive sodium chondrial Precursor; ATP-binding cassette: ATP-Depen channel beta-subunit; Amiloride-sensitive sodium channel dent Clp Protease ATP-Binding Subun; ATP-Dependent delta-Subunit; Amiloride-sensitive sodium channel gamma DNA Helicase: ATP-Dependent Hsl Protease ATP-Binding subunit; Amine Oxidase; Amine Oxidase Flavin-Contain S; ATP-Dependent Metalloprotease Ftsh; ATP-Dependent ing A; Amine Oxidase Flavin-Containing. B; Amine Oxi RNA Helicase P54: ATP-Phosphoribosyltransferase: ATP dase, Copper Containing; Amine Oxidase, Flavin sensitive inward rectifier potassium channel 1: ATP-sensitive Containing; Aminoacylase-1; Aminoglycoside 2'-N- inward rectifier potassium channel 11; Atrial Natriuretic Pep acetyltransferase; Aminoglycoside 3'-Phosphotransferase; tide Clearance Recepto; Atrial natriuretic peptide receptor A: Aminoglycoside 6'-N-Acetyltransferase; Aminomethyl Atrial Natriuretic Peptide Receptor A; Atrolysin C; Aug transferase; Aminopeptidase; Aminopeptidase P, Ami menter Of Liver Regeneration: Aurora-Related Kinase 1: notransferase; Aminotransferase, Putative; Amnionless pro Autocrine Motility Factor; Autoinducer-2 Production Protein tein; AMP deaminase 1: Amp Nucleosidase; AMP-activated Luxs; Autolysin; Auxin Binding Protein 1: Avermectin-Sen protein kinase (AMPK); AMT protein; Amyloid Beta-Pep sitive Chloride Channel GI; Avian Sarcoma Virus Integrase: tide; Amyloid protein-binding protein 1; Amylomaltase; Avidin; Axin; AZurin; B chain; B Lymphocyte Stimulator; Amylosucrase; Anabaena Sensory Rhodopsin; Anaerobic B4-Dimer; B9340; Bacterialazoreductase (Bacillus sp); Bac Ribonucleotide-Triphosphate Reduct; Androgen Receptor; terial isoleucyl-tRNA synthetase; Bacterial Leucyl Ami Angiogenin; Angiostatin; Angiotensin Converting Enzyme; nopeptidase; Bacterial membranes; Bacterial Sialidase; Bac Angiotensin-converting enzyme (ACE); Annexin Al; terial Sulfite Oxidase; Bactericidal/Permeability-Increasing Annexin III; Annexin V: Anthocyanidin Synthase; Anthra Protein; Bacteriochlorophyll A Protein; Bacterioferritin: nilate Phosphoribosyltransferase: Anthranilate Phosphoribo Bacteriophage Lambda Lysozyme; Bacteriophage T4 Short syltransferase 2: Anthrax Toxin Receptor 2: Anti IgE anti Tail Fibre; Bacteriorhodopsin; Baculoviral lap Repeat-Con bodyVH domain chain 1: Anti IgE antibodyVL domain chain taining Protein 4; Bap1; Basement Membrane Protein 1; Antibody Vhh Lama Domain; Antifungal Protein 1: Anti Bm-40; Basic Fibroblast Growth Factor; Basic Phospholi gen 85B; Antigen 85-C; Anti-H; Anti-Muellerian hormone pase A2: Bba1; Bba5: B-cell receptor; Benzoate 1,2-Dioxy type II receptor; Anti-Platelet Protein; Anti-Sigma F Factor genase Reductase; BenZodiazepine Receptor, Benzoylfor Antagonist; Antithrombin III (ATIII); Antithrombin-III: mate Decarboxylase; Benzyl Alcohol Dehydrogenase; Beta 1 Antiviral Protein 3: Antiviral Protein S; Apag Protein; adrenergic receptor, Beta 1.4 Galactosyltransferase; Beta 2 Apc35852; Apc35880; Apical Membrane Antigen 1: Apoc adrenergic receptor; beta chain (FSH); Beta Crystallin B1; arotenoid-Cleaving Oxygenase; Apoferritin Co-Crystallized Beta Lactamase; Beta platelet-derived growth factor receptor With Sn-Protopor; Apolipoprotein; Apollipoprotein A-II; precursor, Beta Trypsin; Beta-(1,3)-glucan synthase Frag Apoptosis regulator Bcl-2; Apoptotic Protease Activating ment: Beta-1,4-D-Glycanase Cex-Cd; Beta-1,4-Galacta Factor 1; Apyrase; Aquaporin 1: Aquaporin Z; Arabinan nase; Beta-1,4-Galactosyltransferase, Beta-1,4-Galactosyl Endo-1,5-Alpha-L-Arabinosidase A: Arabinan-Endo 1.5-Al transferase 1: Beta-1,4-Mannanase; Beta2-Glycoprotein-1; pha-L-Arabinase; Arabinose Operon Regulatory Protein; Beta3 Alcohol Dehydrogenase; Beta-adrenergic receptor Arac, Arachidonate 15-lipoxygenase; Arachidonate 5-li kinase 1: Beta-adrenergic receptor kinase 2: Beta-Agarase A: poxygenase; A-Rafproto-oncogene serine/threonine-protein Beta-Alanine Synthase: Beta-Amylase; Beta-B2-Crystallin; kinase; Arcelin-1 Arcelin-5A; Archaeal Sm-Like Protein Af Beta-Carbonic Anhydrase: Beta-Catenin; BetaChain; Sm2; Archaeosine tRNA-Guanine Transglycosylase; Argin BetaChain (LH); Beta-Conglycinin, Beta Chain; Beta-Cryp ase; Arginase 1: Arginase I; Arginase II; Arginase II, Mito togein; Beta-D-Glucan Exohydrolase Isoenzyme Exo 1: chondrial Precursor, arginine decarboxylase; Arginine Beta-D-Glucan Glucohydrolase Isoenzyme Exo1; Beta-Elic Kinase; Arginine N-Succinyltransferase, Alpha Ch; Argini itin Cryptogein; Beta-Fructosidase; Beta-Galactosidase; noSuccinate Synthase; Argininosuccinate synthase Frag Beta-Galactoside-Binding Lectin; Beta-Glucosidase; Beta ment; Argininosuccinate Synthetase; Arginosuccinate lyase; Glucosidase A. Beta-Glucosyltransferase: Beta-Glucu Arginosuccinate synthase; Aristolochene Synthase; Arnb ronidase; Beta-Hexosaminidase; Beta-Hexosaminidase Beta Aminotransferase; Arno; Aromatase; Aromatic Amino Acid Chain; Beta-Hordothionin; Beta-Hydroxydecanoyl Thiol Aminotransferase; Arpg836; Arsenate Reductase; Arsenical Ester Dehydrase; Betaine-Homocysteine Methyltransferase: pump-driving ATPase; Arsenical Resistance Operon Repres Betaine-Homocysteine S-Methyltransferase: Beta-Keto Acyl Sor, Pu; Arsenite-Translocating Atpase; Arthropodan Carrier Protein Reductase; Beta-Ketoacyl Acyl Carrier Pro Hemocyanin; Artificial Nucleotide Binding Protein; Arto tein Synthas; Beta-Ketoacyl-Acyl-Carrier-Protein Syn carpin; Aryl Sulfotransferase: Arylamine N-Acetyltrans thas; Beta-Ketoacyl-Acp Synthase III: Beta-Ketoacyl-Acyl US 2008/0220441 A1 Sep. 11, 2008 77

Carrier Protein Synth; Beta-Ketoacyl-Acyl Carrier Protein Dependent Protein Kinase; cAMP Phosphodiesterase: Synthase; Beta-Ketoacylsynthase III: Beta-Lactam Syn Camp-Dependent Protein Kinase; Camp-Dependent Protein thetase; Beta-Lactamase; Beta-Lactamase CtX-M-14; Beta Kinase Regulatory Sub; Camp-Dependent Protein Kinase Lactamase CtX-M-27; Beta-Lactamase CtX-M-9; Beta-Lac Type 1; Camp-Dependent Protein Kinase Type I-Alpha R: tamase II: Beta-Lactamase Imp-1: Beta-Lactamase Oxa-1: Camp-Dependent Protein Kinase, Alpha-Cat; Camp-Specific Beta-Lactamase Oxa-10; Beta-Lactamase Oxa-2: Beta-Lac 3',5'-Cyclic Phosphodieste; Camp-Specific 3',5'-Cyclic Phos tamase Pse-2, Beta-Lactamase ShV-1; Beta-Lactamase Shv phodiesterase; cAMP-specific 3',5'-cyclic phosphodiesterase 2. Beta-Lactamase Tem; Beta-Lactamase. Type II: Beta-Lac 7B; Camp-Specific Phosphodiesterase Pde4D2: Cannabinoid toglobulin; Beta-Mannanase; Beta-Mannosidase; Beta receptor 2; Cannabinoid Receptors; Capsid Protein C; Capsid Methylaspartase; Beta-Momorcharin; Beta-N- Protein P40; Capsid Protein P40: Assemblin Protease; Cara: Acetylhexosaminidase; Beta-N-Acetylhexosaminidase; Carbapenem Synthase; Carbohydrate-Phosphate Isomerase: Beta-Phosphoglucomutase; Beta-Purothionin; Beta-Secre Carbon Monoxide Oxidation System Transcripti; Carbonic tase 1: Beta-Spectrin; Beta-Trypsin; Beta-Tryptase; Bho236 Anhydrase; Carbonic Anhydrase I; Carbonic Anhydrase II; Protein; Bifunctional 3'-Phosphoadenosine 5'-Phospho: Carbonic Anhydrase III; Carbonic Anhydrase IV: Carbonic Bifunctional adenosylcobalamin biosynthesis protein cobU: Anhydrase Xii; Carbonic Anhydrase Xiv; Carbonyl Reduc Bifunctional aminoacyl-tRNA synthetase: Bifunctional tase; Carbonyl Reductase Nadph 1; Carboxy Methyl Trans Deaminase/Diphosphatase: Bifunctional Dihydrofolate ferase For Protein Phosp; Carboxy-Cis.Cis-Muconate Reductase-Thymidy; Bifunctional dihydrofolate reductase Cyclase; Carboxyethylarginine Synthase; Carboxylesterase: thymidylate synthase: Bifunctional Histidine Biosynthesis Carboxylesterase Est2: Carboxylesterase Precursor; Car Prot; Bifunctional methylenetetrahydrofolate dehydroge boxymethylated Rhodanese: Carboxymuconolactone Decar nase/cyclohydrolase; Bifunctional P450: Nadph-P450 boxylase Family Pr; Carboxypeptidase A. Carboxypeptidase Reductase: Bifunctional PGK/TIM Includes: Phosphoglyc Gp180 Residues 503-882: Carboxypeptidase M: Carboxy erate kinase, EC 2.7.2.3, Triosephosphate isomerase, EC5.3. Terminal Domain RNA Polymerase I; Caminomycin 4-O- 1.1, TIM, Triose-phosphate isomerase: Bifunctional Purine Methyltransferase; Carnitine Acetyltransferase; Carnitine Biosynthesis Protein Pur: Bifunctional purine biosynthesis Acetyltransferase Isoform 2; Carnitine O-acetyltransferase: protein PURH Includes: Phosphoribosylaminoimidazole Carnitine O-palmitoyltransferase I, mitochondrial liver iso carboxamide formyltransferase, EC 2.1.2.3, AICAR trans form (CPT-1); Carnitine O-palmitoyltransferase II, mito formylase, IMP cyclohydrolase, EC 3.5.4.10, Inosinicase, chondrial (CPT-2); Casein Kinase II, Alpha Chain; Casein IMP synthetase, ATIC: Bifunctional Puta Protein: Bifunc Kinase-1; Caspase-1 precursor; Caspase-3; Caspase-7: Cata tional Rela/Spot; Bikunin; Bile Acid Receptor; Bile salt bolic Alanine Racemase Dadx; Catabolite Gene Activator; export pump; Bile-Salt Activated Lipase; Biliary Glycopro Catabolite Gene Activator Protein; Catalase; Catalase 1: tein C; Bilin Binding Protein; Bilin-Binding Protein; Biliver Catalase A: Catalase Hpii; Catalase-Peroxidase; Catalase din IX Beta Reductase; Biliverdin Reductase A; Biliverdin Peroxidase Protein Katg; Catechol 1,2-Dioxygenase; Cat reductase A precursor: Bioh Protein; Biosynthetic Thiolase; echol Oxidase; Catechol-O-Methyltransferase: Catechol-O- Biotin Synthase; biotinidase; biotin-protein ligase; Biphenyl methyltransferase (COMT): Cathepsin B: Cathepsin F; 2,3-Diol 1,2-Dioxygenase; Bleomycin Resistance Determi Cathepsin G: Cathepsin K; Cathepsin S: Cathepsin V: Cation nant; Bleomycin Resistance Protein; Bleomycin-Binding Dependent Mannose-6-Phosphate Recepto: Cation-Depen Protein; Blood Coagulation Factor Vii; Blue Fluorescent Pro dent Mannose-6-Phosphate Recepto: Cationic amino acid tein; B-Luffin; Bm-40; Bone Marrow Stromal Cell Antigen 1: transporter-3; Cationic amino acid transporter-4; Cation-In Bone Morphogenetic Protein 2: Bone Morphogenetic Protein dependent Mannose 6-Phosphate Recep: Cbp21; Cd2; CD2 7; Botulinum Neurotoxin Type B; Bovine Beta-Lactoglobu lymphocyte antigen; CD20 B-lymphocyte antigen; CD33 lin A; Bowman-Birk Inhibitor Derived Peptide; Bp40; Brady antigen; Cd46; CD52 Antigen; Cd58; Cd59 Complexed With kinin; B-Raf proto-oncogene serine/threonine-protein Glcnac-Beta-1,4-Glcnac-Be; Cdc25 B-Type Tyrosine Phos kinase; Branched-chain alpha-ketoacid dehydrogenase phatase; Cdc42Hs-GDP; Cdp-Glucose 4,6-Dehydratase: kinase; Branched-Chain Amino Acid Aminotransferase; Cdp-Glucose-4,6-Dehydratase; Cdp-Tyvelose-2-Epimerase: Branched-Chain Amino Acid Aminotransferase, Branched CEA or carcinoembryonic antigen-multiple sequences; Cell chain-amino-acid aminotransferase, cytosolic; Branched Cycle Arrest Protein Bub3; Cell Division Control Protein 2 chain-amino-acid aminotransferase, mitochondrial; Homolog: Cell Division Control Protein 6: Cell Division Brazzein; Bruton S Tyrosine Kinase; BseG341 Restriction Inhibitor; Cell Division Protein Ftsy: Cell division protein Endonuclease; Butyryl-Coa Dehydrogenase; C Protein ftsz. Cell Division Protein FtsZ. Homolog 1: Cell Division Alpha-Antigen; C. pasteurianum Hydrogenase I: C-1027 Protein Kinase 2: Cell Division Protein Kinase 7: Cell Divi Apoprotein; C1R Complement Serine Protease: C-1-tetrahy sion Protein Zipa: Cell Wall Pentapeptide Ala-: Cell Wall drofolate synthase: C-4 methylsterol oxidase; C4-Dicarboxy Peptide In Complex With Deglucobalhi: Cellobiohydrolase; late Transport Transcriptional R; Caffeic Acid 3-O-Methyl Cellobiohydrolase CeléA; Cellobiohydrolase I: Cellobiohy transferase; Caffeoyl-Coa O-Methyltransferase: Cag-Z: drolase I Catalytic Domain: Cellobiohydrolase II: Cellobiose Calcineurin B subunit isoform 1: Calcineurin B-Like Protein Dehydrogenase; Cellular retinaldehyde-binding protein: Cel 4, Calcitonin, Calcitonin Analogue; Calcitonin receptor, Cal lular retinoic acid binding protein 1: Cellular retinoic acid cium/Calmodulin-Dependent 3',5'-Cycli; Calcium/Calm binding protein 2: Cellulase; Cellulase B: Cellulase Cel48F: odulin-Dependent Protein Kinase; calcium-activated potas Cellulase Cel9M; Cellulase Celc: Cellulomonas Fimi Family sium channel; Calcium-binding mitochondrial carrier protein 10 Beta-1,4-Glycana; Cellulosomal Scaffoldin; Cephaibol B; Aralarl; Calcium-binding mitochondrial carrier protein Cephalosporin C Deacetylase; Cephalosporinase; Ceramide Aralar2: Calcium-Dependent Protease, Small Subunit; Cal glucosyltransferase: Ceruloplasmin Cg 14704 Protein; coMP cium-transporting ATPase type 2C member 1, CalgizZarin; Phosphodiesterase; Cgmp Phosphodiesterase A2; Cgmp-In Calmodulin, Calpain 1, Large Catalytic Subunit; Camp hibited 3',5'-Cyclic Phosphodiesteras; Cgmp-Specific 3',5'- US 2008/0220441 A1 Sep. 11, 2008

Cyclic Phosphodiesterase: Chalcone Synthase; Chalcone Constitutive Androstane Receptor; Contryphan-R: Contry Synthase 2: Chalcone-Flavonone Isomerase 1: Chalcone-Fla phan-Sm; Contryphan-Vn, Major Form: Copper Amine Oxi Vonone Isomerase 1: Chaperone Protein Htpg: C-Ha-Ras: dase; Copper Amine Oxidase; Copper Amine Oxidase, Liver Charybdotoxin; Chemosensory Protein A6; Chemotactic Isozyme: Copper Transport Protein Atox1; Copper-Contain Peptide; Chemotaxis Protein Chea; Chemotaxis Protein ing Nitrite Reductase; Core Protein; Corticosteroid 11-Beta Chey; Chemotaxis Receptor Methyltransferase Cher; Chi Dehydrogenase Isozyme: Corticosteroid 11-Beta-Dehydro mera Of Glutathione S-Transferase-Synthet: Chimera Of genase, Isozym; Corticosteroid 11-beta-dehydrogenase, Maltose-Binding Periplasmic Prote: Chitinase; Chitinase; isozyme 1: Corticosteroid 11-beta-dehydrogenase, isozyme Chitinase 1: Chitinase A; Chitinase A; Chitinase B: Chitinase 2: Corticosteroid Receptor; Corticotropin Releasing Hor B: Chitinase-3 Like Protein 1; Chitobiase; Chitobiose Phos mone: COX-1: COX-2; Crabp-I: Crca Protein; C-Reactive phorylase; Chitosanase; Chitotriosidase; Chitotriosidase 1: Protein; Creatine kinase B-type; Creatine kinase M-type: Chitotriosidase Synonym: Chitinase; Chloramphenicol Creatine Kinase, B Chain; Creatine kinase, sarcomeric: Cre Acetyltransferase; Chloramphenicol Phosphotransferase: atine kinase, ubiquitous; Crk-Associated Substrate; Crotono Chlorella Virus DNA Ligase-Adenylate; Chloride channel betainyl-Coa: Carnitine Coa-Trans; Crotonobetainyl-Coa: protein 2: Chloride Intracellular Channel Protein 1: Chloro Carnitine Coa-Transfera; Crustacyanin; Crustacyanin A1 catechol 1,2-Dioxygenase; Chloroperoxidase; Chloroperoxi Subunit; Crustacyanin C2 Subunit; Cruzipain; Cryptochrome dase F. Chlorophyll A-B Binding Protein Ab80; Chlorophyll 1 Apoprotein: Csdb: Csdb Protein; C-Terminal Analogue Of A-B Binding Protein, Chloroplast; Chloroplast Ferredoxin Neuropeptide Y. A; C-Terminal Binding Protein 1: C-Termi Nadp+ Oxidoreductase; Chloroplast Outer Envelope Protein nal Binding Protein 3; C-Terminal Src Kinase; Ctla-4: Ctp Oep34; Chloroplastic Ascorbate Peroxidase; Cho Reductase: Synthase; Ctp: Phosphocholine Cytidylyltransferase: C-Type Cholecystokinin type A receptor; Cholera Toxin: Cholera Lectin Dc-Signr, Cutinase; Cyan Fluorescent Protein Cfp: Toxin B Subunit; Cholesterol Esterase; Cholesterol Oxidase; Cyanate Lyase; Cyanoglobin; Cyanovirin-N; Cyclic Alpha Choline dehydrogenase; Choline kinase alpha; Choline Melanocyte Stimulating Hormo: Cyclic Hexapeptide Rr; O-acetyltransferase: Choline/ethanolamine kinase; Choline Cyclic Parathyroid Hormone; Cyclic Phosphodiesterase: phosphate cytidylyltransferase A. Choline-phosphate cytidy Cyclin Dependent Kinase Subunit, Type 1: Cyclin-Depen lyltransferase B: Cholinesterase; Choloylglycine Hydrolase; dent Protein Kinase 2: Cyclo: Cyclodextrin Glycosyltrans Chondroitin Ac Lyase; Chondroitinase Ac; Chondroitinase ferase: Cyclodextrin-Glycosyltransferase: Cyclomaltodex B: Chorionic Gonadotropin: Chorismate Lyase; Chorismate trin Glucanotransferase; Cyclooxygenase-2; Cyclophilin; Mutase; Chorismate Synthase; Chromosomal Replication Cyclopropane-Fatty-Acyl-Phospholipid Syn: Cyclopropane Initiator Protei: Chymase; Chymase; Chymotrypsin; chymot Fatty-Acyl-Phospholipid Synthas; Cyclopropane-fatty-acyl rypsin B: Chymotrypsinogen A; Circadian Clock Protein phospholipid synthase 1: Cyclosporin A As Bound To Cyclo Kaib; Cis-Biphenyl-2,3-Dihydrodiol-2,3-Dehydrogena Cite: philin: Cyp175A1: CYP1A2: Cystalysin; Cystathionine Citrate Lyase. Beta Subunit; Citrate Synthase: Citrate Syn Beta-Synthase; CyStathionine gamma-lyase. CyStathionine thase: C-Kit Protein; Claret Segregational Protein; Class B Gamma-Synthase; Cysteine desulfurase: Cysteine dioxyge Acid Phosphatase; Class B Carbapenemase Blab-1; Class C nase fragment: Cysteine dioxygenase type I: Cysteine Beta-Lactamase; Class I Alpha-1,2-Mannosidase; Class-Mu sulfinic acid decarboxylase; Cysteine-Rich Domain Of Man Glutathione S-Transferase; Clavaminate Synthase 1: Clpb nose Receptor; Cysteinyl leukotriene Receptor 1: Cysteinyl Protein; Cmp-N-Acetylneuraminic Acid Synthetase; Coagul leukotriene receptor 2: Cysteinyl-tRNA Synthetase: Cystic lation Factor Ix; Coagulation Factor V: Coagulation factor Fibrosis Transmembrane Conductanc: Cystic Fibrosis Trans VII: Coagulation Factor VIII; Coagulation Factor Viii Precur membrane Conductance Re: Cystine/glutamate transporter; sor; Coagulation Factor X: Coagulation Factor Xiii; Coagul Cystinosin; Cytidine Deaminase; Cytidine Monophospho-N- lation Factor XiiiA Chain; Coagulation factor XIII A chain Acetylneuraminic Acid; Cytidylate Kinase; Cytochrome precursor; Coat Protein; Coatomer Gamma Subunit; Cob: B=5=Reductase; Cytochrome B2; Cytochrome B2, Mito Cob(I)yrinic acid a,c-diamide adenosyltransferase; Cobal chondrial; Cytochrome B5; Cytochrome B5 Outer Mitochon amin-Dependent Methionine Synthase; Cobalt-Precorrin-4 drial Membrane Is; Cytochrome B562; Cytochrome C: Cyto Transmethylase; Cocaine Esterase: Coenzyme A Biosynthe chrome C". Cytochrome C"; Cytochrome C Family Protein; sis Bifunctional Protein: Coenzyme F420-Dependent Cytochrome C Nitrite Reductase; Cytochrome c oxidase sub N5.N10-Methylenete: Coenzyme F420H2: Nadp+ Oxi unit 1; Cytochrome CPeroxidase; Cytochrome CPeroxidase, doreductase: Coenzyme Paq Synthesis Protein C: Cog4826: Mitochondrial; Cytochrome C, Iso-1; Cytochrome C. Puta Serine Protease Inhibitor; Collagen; Collagenase 3: Collage tive: Cytochrome C2; Cytochrome C2, Iso-2; Cytochrome nase-3; Collagen-Like Peptide; Complement C1R Compo C3: Cytochrome C3, A Dimeric Class III C-Type Cy; Cyto nent; Complement C1S Component; Complement C3Dg: chrome C4; Cytochrome C549; Cytochrome C550; Cyto Complement Control Protein; Complement Decay-Acceler chrome C551; Cytochrome C-551; Cytochrome C551 Per ating Factor; Complement Factor B: Complement Protein oxidase; Cytochrome C552; Cytochrome C-552; C8Gamma; Complement Receptor Type 2: COMT (catecol Cytochrome C-553; Cytochrome C-554; Cytochrome C-556; O-methyl-transferase); Conantokin-T: Conantoxin G. Con Cytochrome C6: Cytochrome C7: Cytochrome Cd1 Nitrite gerin I; Congerin II: Conjugal Transfer Protein Trwb: Con Reductase; Cytochrome CI; Cytochrome F: Cytochrome nective Tissue Activating Peptide-III: Conotoxin Gs: Oxidase Subunit II: Cytochrome P450; Cytochrome P450 Conserved Hypothetical Protein; Conserved Hypothetical 107A1; Cytochrome P450 1 19; Cytochrome P450 121; Cyto Protein Af2008: Conserved Hypothetical Protein Mth1747; chrome P450 152A1; Cytochrome P450 154C1; Cytochrome Conserved Hypothetical Protein Tm 1158: Conserved Hypo P450 17A1; Cytochrome P450 19 (Aromatase); Cytochrome thetical Protein Tm 1464; Conserved Hypothetical Protein P450 27: Cytochrome P450 2B4; Cytochrome P450 2C5; Ydce: Conserved Hypothetical Protein Yffb; Conserved Cytochrome P4502C8: Cytochrome P450 2C9; Cytochrome Hypothetical Protein Yuaa; Conserved Protein Mth1675: P450 2R1; Cytochrome P450 3A4; Cytochrome P450 4A11 US 2008/0220441 A1 Sep. 11, 2008 79 precursor; Cytochrome P450 51; Cytochrome P450 51 orotase; Dihydroorotate Dehydrogenase; Dihydroorotate (Yeast); Cytochrome P450 55A1; Cytochrome P450 Bm-3: Dehydrogenase A; Dihydroorotate Dehydrogenase, mito Cytochrome P450 Cyp119; Cytochrome P450 CYP11B1 chondrial Precursor: dihydropterate synthase (bacterial); (steroid hydroxylase); Cytochrome P450Cam; Cytochrome Dihydropteridine Reductase: Dihydropteridine Reductase: P450-Cam; Cytochrome P450Epok; Cytochrome P450Eryf: Dihydropteroate synthase: Dihydropteroate Synthase (ma Cytochrome P450Nor; Cytochrome Rc557: Cytoglobin: larial); Dihydropteroate synthase (Pneumocystis carinii); Cytohesin 2: Cytokine Receptor Common Beta Chain; Cyto Dihydropteroate Synthase I: Dihydropyridine calcium chan kinin Dehydrogenase 1: Cytosine Deaminase; cytosolic nel; Dihydropyridine-sensitive L-type, calcium channel 5-nucleotidase II; Cytosolic phospholipase A2; Cytotoxic T alpha-2/ delta Subunits; Dihydropyrimidine dehydrogenase; Lymphocyte Associated Antigen 4; Cytotoxic Tcell Valpha Dihydroxyacetone Kinase; Diisopropylfluorophosphatase; Domain; Cytotoxin 3: D(1B) dopamine receptor; D(2) Dimeric Hemoglobin: Dimethyl Sulfoxide Reductase: Dopamine Receptor; D(3) Dopamine Receptor; D(4) dopam Dipeptidyl Aminopeptidase-Like Protein 6: Dipeptidyl Pep ine receptor, D1 dopamine receptor-interacting protein cal tidase I Dipeptidyl Peptidase IV: Dipeptidyl Peptidase IV: cyon: D199S Mutant Of Bovine 70 Kilodalton Heat Sh; Dipeptidyl Peptidase IV Soluble Form; Diphtheria Toxin; D206S Mutant Of Bovine 70 Kilodalton Heat Sh; D-2-Hy Diphtheria Toxin Repressor; Diphthine Synthase: Dissimila droxyisocaproate Dehydrogenase; D3, D2-Enoyl Coa tory Copper-Containing Nitrite: Dissimilatory Copper-Con Isomerase Ecil; D-3-Phosphoglycerate Dehydrogenase; taining Nitrite Redu; D-lactate dehydrogenase: D-Lactate D-3-Phosphoglycerate Dehydrogenase; Dabd; Dahp Syn Dehydrogenase; Dlp-1: D-Maltodextrin-Binding Protein; thetase: D-Ala: D-Ala Ligase: D-Alanine Aminotransferase; Dmso Reductase; DNA Adenine Methylase; DNA Beta-Glu D-Alanine: D-Lactate Ligase: D-alanine-D-alanine ligase A: cosyltran?ferase; DNA Cytosine Methyltransferase Dnmt2: D-Alanyl-D-Alanine Carboxypeptidase; D-Amino Acid DNA Double-Strand Break Repair RadS0 Atpase; DNA Aminotransferase: D-Amino Acid Oxidase, D-amino-acid Gyrase B; DNA gyrase subunit A; DNA Gyrase Subunit B; oxidase; D-Aminoacylase; Dape:; Daptomycin; D-beta-hy DNA Helicase; DNA Ligase; DNA Ligase I: DNA Ligase III; droxybutyrate dehydrogenase, mitochondrial precursor; DNA Ligase, Nad-Dependent; DNA Ligase, Nad-Depen Dcoh: Ddab: De Novo Designed 21 Residue Peptide; De dent; DNA Mismatch Repair Protein Mutl; DNA Nucleotide Novo Designed Cyclic Peptide; Deacetoxycephalosporin C Excision Repair Enzyme Uvrb; DNA Photolyase; DNA Poly Synthase: Death-Associated Protein Kinase; Death-Associ merase; DNA Polymerase (human cytomegalovirus); DNA ated Protein Kinase 1: Decorin: Dehaloperoxidase; Dehydro polymerase (human herpes simplex virus 1); DNA Poly genase/reductase SDR family member 4: Delta 2 Crystallin: merase (human); DNA polymerase (Varicella-zoster virus); Delta Crystallin I; Delta Crystallin II; Delta-1-pyrroline-5- DNA Polymerase alpha (human); DNA Polymerase Beta; carboxylate dehydrogenase, mitochondrial precursor, Delta DNA Polymerase I: DNA Polymerase III Subunit Gamma; Aminolevulinic Acid Dehydratase: Delta-Conotoxin Evia; DNA Polymerase III, Epsilon Chain; DNA Primase; DNA Deoxycytidine Kinase; Deoxycytidine Triphosphate Deami Primase Small Subunit; DNA Primase/Helicase; DNA Repair nase; Deoxycytidylate Deaminase; Deoxycytidylate and Recombination Protein Rad; DNA Repair and Recombi Hydroxymethylase; Deoxy-D-Mannose-Octulosonate nation Protein Rada; DNA Repair Protein Xrcc4; DNA Rep 8-Phosphate Pho; Deoxyhypusine Synthase; Deoxyhypusine lication Protein; DNA Topoisomerase I: DNA Topoisomerase Synthase: Deoxynucleoside Monophosphate Kinase; Deox II; DNA Topoisomerase II (bacterial); DNA-3-Methylad yribodipyrimidine Photolyase; Deoxyribonuclease I: Deox enine Glycosylase I: DNA-3-Methyladenine Glycosylase II; yribonucleoside Kinase; Deoxyribose-Phosphate Aldolase; DNA-Binding Response Regulator; DNA-directed RNA Deoxyuridine 5'-Triphosphate Nucleoditohydro: Deoxyuri polymerase (E. coli); DNA-directed RNA polymerase beta dine 5'-Triphosphate Nucleotide Hydr; Deoxyuridine chain; DNA-directed RNA polymerase beta' chain; DNA 5'-Triphosphate Nucleotidohydro: Deoxyuridine Triphos Directed RNA Polymerase Subunit L: Dodecin. DOPA phatase; Dephospho-Coa Kinase; Der F II: DesGly1 Decarboxylase; Dopamine beta hydroxylase; Dopamine D1 Contryphan-R: Designed Protein Ctpr2: Designed Protein Receptor, Dopamine reuptake pump; Dp-Tt2; Dr Hemagglu Ctpr3: Dethiobiotin Synthetase; Devb Protein: Dextranase; tinin Structural Subunit; D-Ribose-5-Phosphate Isomerase: D-Galactose)-GLUCOSE BINDING PROTEIN; D-Glu D-Ribose-Binding Protein Complexed With Beta; D-Ribose cose 6-Phosphotransferase: D-Glyceraldehyde-3-Phosphate Binding Protein Mutant With Gly 134; D-Ribose-Binding Dehydrogena: D-Glyceraldehyde-3-Phosphate Dehydroge Protein Mutant With Ile 132: Drosophila Neuroglian; Dtdp nase, D-Glyceraldehyde-3-Phosphate-Dehydrogena; 4-Dehydrorhamnose 3.5-Epimerase: Dtdp-4-Dehydrorham D-Glyceraldehyde-3-Phosphate-Dehydrogenase; Dhps, nose Reductase, Rfbd O: Dtdp-6-Deoxy-D-Xylo-4-Hexylose Dihydropteroate Synthase: D-Hydantoinase; Diacylglycerol 3.5-Epimerase: Dtdp-D-Glucose 4,6-Dehydratase; Dtdp kinase; Diadenosine Tetraphosphate Hydrolase; Diamine Glucose Oxidoreductase: Dual Adaptor Of Phosphotyrosine acetyltransferase 1; Diamine acetyltransferase 2: Diami and 3-Phosp: Dual Specificity Mitogen-Activated Protein K: nopimelate Decarboxylase; Dianthin 30; Dienelactone Dual Specificity Protein Kinase Clk1; Duck Ovotransferrin; Hydrolase; Dienoyl-Coa Isomerase; Diga16: Di-Haem Cyto Duodenase; Dutp Pyrophosphatase: D-Xylose Isomerase: E. chrome C Peroxidase; Diheme Cytochrome C Napb: Di coli citrate synthetase; E. coli glutathione reductase; E. coli Heme Peroxidase; Dihydrodipicolinate Reductase; Dihy malate dehydrogenase; E. Coli Maltodextrin Phosphorylase; drodipicolinate Reductase; Dihydrodipicolinate Synthase: E. coli pyruvate dehydrogenase; E. coli ribosomal proteins; Dihydrofolate Reductase; Dihydrofolate Reductase (ma Eafp 2: Early Endosomal Autoantigen 1: Ecotin: Eh Domain larial); Dihydrolipoamide Dehydrogenase; Dihydrolipoyl Binding Protein Epsin; Eif2Gamma; Elastase; Elastase 1: dehydrogenase, mitochondrial precursor, Dihydrolipoyl Eledoisin; Elongation Factor: Elongation Factor 1-Alpha; Transacetylase, Dihydrolipoyllysine-residue acetyltrans Elongation Factor 2: Elongation Factor G; Elongation Factor ferase component of pyruvate dehydrogenase complex, mito G Complexed With Guanosine; Elongation Factor Tu; Endo/ chondrial precursor; Dihydroneopterin Aldolase; Dihydro Exocellulase E4, Endo-1,4-B-D-Mannanase; Endo-1,4-Beta US 2008/0220441 A1 Sep. 11, 2008

Glucanase Engf; Endo-1,4-Beta-D-Xylanase; Endo-1,4- Acid-Binding Protein, Adipocyte; Fatty Acid-Binding Pro Beta-Glucanase; Endo-1,4-Beta-Glucanase F. Endo-1,4- tein, Brain; Fatty acid-binding protein, liver; Fatty aldehyde Beta-Xylanase; Endo-1,4-beta-Xylanase 2 precursor, Endo dehydrogenase; Fatty-Acid Amide Hydrolase. F-Box Only 1,4-Beta-Xylanase A: Endo-1,4-Beta-Xylanase A Precursor: Protein 2: Fc Fragment; Fc Gamma Receptor FCGR1 HU Endo-1,4-Beta-Xylanase II: Endo-1,4-Beta-Xylanase Y: MAN: Feglymycin; Feline Immunodeficiency Virus Pro Endo-Alpha-Sialidase; Endo-Beta-1,4-Glucanase; Endo tease: Feline Leukemia Virus Receptor-Binding Domai; Beta-N-Acetylglucosaminidase F3; Endocellulase E1; Endo Ferredoxin; Ferredoxin II; Ferredoxin Reductase; Ferre glucanase; Endoglucanase 5A: Endoglucanase 9G. Endoglu doxin: Nadp+ Oxidoreductase: Ferredoxin: Nadp+ Reduc canase A: Endoglucanase B; Endoglucanase C. tase; Ferredoxin-Dependent Glutamate Synthase: Ferre Endoglucanase I: Endoglucanase I: Endoglucanase V Cello doxin-Nadp Reductase: Ferredoxin-Nadip Reductase: biose Complex: Endoplasmic Reticulum Mannosyl-Oli Ferredoxin-Nadp+ Reductase: Ferredoxin-Nadp+ Reduc gosacchari; Endoplasmin, Endopolygalacturonase; Endopo tase; Ferric Hydroxamate Receptor; Ferric Hydroxamate lygalacturonase; EndoSome-Associated Protein; Endothelial Uptake Receptor; Ferrichrome-Binding Periplasmic Protein; Nitric-Oxide Synthase: Endothelial Protein C Receptor; Ferrichrome-Iron Receptor; Ferrichrome-Iron Receptor Pre Endothelin B receptor precursor; Endothelin-1; Endothelin-1 cursor; Ferripyochelin Binding Protein: Ferripyoverdine receptor precursor, Endothiapepsin, Endothiapepsin precur Receptor, Ferritin heavy chain; Ferritin light chain; Ferroche sor; Endoxylanase; Endoxylanase 1 1A: Engrailed Home latase: Feruloyl Esterase A; Fez-1 Beta-Lactamase; Fgf odomain; Enhancing Lycopene Biosynthesis Protein; Receptor 1: Fiber Protein: Fibrin; Fibrinogen-420; Fibroblast Enkephalinase; Enolase; Enolase 1: Enoyl Acp Reductase: Activation Protein, Alpha Subunit; Fibroblast Growth Factor Enoyl Acyl Carrier Protein Reductase; Enoyl-Acyl-Carrier 9; Fibroblast Growth Factor Receptor 2: Fibroblast growth Protein Reductase: Enoyl-Acyl-Carrier-Protein Reduc factor-4 precursor: Fibronectin; Fimbrial Lectin; Fk506 tase; Enoyl-Acyl-Carrier-Protein Reductase: Enoyl-Acyl Binding Protein: Fk506-Binding Protein: FK506-binding Carrier-Protein Reductase Nadh: Enoyl-acyl-carrier-pro protein 1A: Fk506-Binding Protein 4; Fkbp 12.6; FKBP12 tein reductase NADH: Enoyl-Acp Reductase: Enoyl-Acp rapamycin complex-associated protein; Fkbp25; Fkbp-Type Reductase: Enoyl-Acyl Carrier Protein; Enoyl-Coa Peptidyl-Prolyl Cis-Trans Isom; Fksg76; FL cytokine recep Hydratase: Enoyl-Coa Hydratase, Mitochondrial; Envelope tor precursor: Flavin reductase: Flavocytochrome B2: Flav Glycoprotein; Envelope Glycoprotein; Envelope glycopro ocytochrome C: Flavocytochrome C Fumarate Reductase: tein GP340; Envelope glycoprotein GP340/GP220; Eosino Flavocytochrome C3; Flavocytochrome C3 Fumarate Reduc phil Cationic Protein; Eosinophil Lysophospholipase Chain: tase: Flavodoxin; Flavodoxin Reductase: Flavohemoprotein; A: Eosinophil-Derived Neurotoxin; Ep-Cadherin; Ephrin Flavoprotein; Fluorescent Protein Fp538; Fmn-Binding Pro Type-A Receptor 2; Ephrin-A5; Ephrin-B2: Epidermal tein; Fms 1 Protein; Focal Adhesion Kinase 1: Folate receptor Growth Factor: Epidermal Growth Factor Receptor; Epider alpha; Folate receptor beta; Folate receptor gamma; Folate mal Growth Factor Receptor 2: Epidermal growth factor transporter 1: Folc Bifunctional Protein; Follicle Stimulating receptor precursor: Epidermin Modifying Enzyme Epid; Epi Hormone Receptor; Follistatin: Folylpolyglutamate syn didymal Secretory Protein E1 Epilancin 15X; Epoxide thase; Folylpolyglutamate synthase, mitochondrial; Hydrolase: Epoxide Hydrolase 2, Cytoplasmic; Epsin; Epsp Folylpolyglutamate Synthetase: Formaldehyde Dehydroge Synthase: Ergosterol biosynthetic protein 28; Ermc' Methyl nase; Formaldehyde Ferredoxin Oxidoreductase: Formalde transferase; Erv2 Protein, Mitochondrial; Erythrina Crista hyde-Activating Enzyme Fae; Formate Acetyltransferase 1: Galli Lectin; Erythropoietin receptor, Esal Histone Acetyl Formate Dehydrogenase H; Formiminotransferase-Cy transferase; Esal Protein: E-Selectin; Esta; Esterase; clodeaminase; Formyl-Coenzyme A Transferase; Formylme Estradiol 17 Beta-Dehydrogenase 1: Estradiol 17 Beta-De thionine Deformylase: Four-Helix Bundle Model; Fpra; Fr-1 hydrogenase 4: Estradiol 17-beta-dehydrogenase 1: Estradiol Protein; Fragile Histidine Protein; Fragile Histidine Triad 17-beta-dehydrogenase 2: Estradiol 17-beta-dehydrogenase Protein; Fructan 1-Exohydrolase Iia; Fructose 1,6-Bisphos 3: Estradiol 17-beta-dehydrogenase 8: Estrogen Receptor; phatase. Fructose 1,6-Bisphosphatase/Inositol Monopho: Estrogen Receptor (ER); Estrogen Receptor Alpha; Estrogen Fructose 1,6-Bisphosphate Aldolase; Fructose-1,6-Bis; Fruc Receptor Beta: Estrogen Sulfotransferase; Estrogen-Related tose-1,6-Bisphosphatase; Fructose-2,6-Bisphosphatase; Receptor Gamma; Eukaryotic Peptide Chain Release Factor Fructose-Bisphosphate Aldolase; Fructose-Bisphosphate GTP-, Eukaryotic Translation Initiation Factor 4E: Evolved Aldolase A. Fructose-Bisphosphate Aldolase Class I; Fruc beta-galactosidase alpha-Subunit; Excinuclease Abc Subunit tose-Bisphosphate Aldolase II; FtsZ. Fucose-Specific Lectin; B; Exo-; Exocellobiohydrolase I: Exoglucanase I: Exo-Inuli Fumarase C; Fumarate Hydratase Class II; Fumarate reduc nase; Exo-Maltotetraohydrolase; Exopolyphosphatase; Exo tase flavoprotein subunit; Fumarylacetoacetate Hydrolase; toxin A: Expressed Protein; Exterior Membrane Glycopro Fusion Protein; Fusion Protein Consisting Of Kinesin-Like tein Gp120; Extracellular calcium-sensing receptor Pr; Fusion Protein Consisting Of Staphylococcus: Fv Frag precursor: Extracellular Regulated Kinase 2: Extracellular ment; G Protein Gi Alpha 1: G15-Gramicidin A; G25K GTP Signal-Regulated Kinase 2: Extracellular Subtilisin-Like Binding Protein; GABA Transaminase; GABA-A Receptor; Serine Protein: Extrahepatic lipoprotein lipase (LL); F17-Ag GABA-B Receptor; Gag Polyprotein; Gall0 Bifunctional Lectin; F1-Gramicidin A; F1-Gramicidin C: F420-Depen Protein; Galactanase; Galactokinase; Galactose Mutarotase; dent Alcohol Dehydrogenase; F65AY131C-Mi Carbonic Galactose Oxidase; Galactose Oxidase Precursor; Galactose Anhydrase V: Factor D: Factor IIIFactor IX Factor VIIIFactor 1-Phosphate Uridyl Transferase-Lik; Galactose-1-Phosphate X; Factor Inhibiting Hifl; Farnesyl Diphosphate Synthase: Uridylyltransferase; Galactose-Binding Protein Complex Farnesyl pyrophosphate synthetase; Fasciclin I; Fatty Acid With Gluco; Galactose-Specific Lectin; Galactoside Binding Protein; Fatty Acid Binding Protein Homolog; Fatty O-Acetyltransferase; Galactosylgalactosylxylosylprotein Acid Metabolism Regulator Protein; Fatty Acid/Phospho 3-Beta-G: Galectin-1; Galectin-1; Galectin-2: Galectin-3, lipid Synthesis Protei: Fatty Acid-Binding Protein; Fatty Galectin-3; Galectin-7: Gamma Chymotrypsin; Gamma US 2008/0220441 A1 Sep. 11, 2008

Aminobutyrate Metabolism Dehydratase/I: Gamma-ami Glutamyl-Endopeptidase; Glutamyl-tRNA Reductase: nobutyric-acid receptor alpha-2 Subunit precursor; Gamma Glutamyl-tRNA Synthetase: Glutaredoxin 3: Glutaryl-Coa aminobutyric-acid receptor alpha-3 subunit precursor, Dehydrogenase; Glutathine Synthetase; Glutathione Reduc Gamma-aminobutyric-acid receptor alpha-4 subunit precur tase; Glutathione reductase (mitochondrial); Glutathione sor; Gamma-aminobutyric-acid receptor alpha-5 subunit pre S-Transferase; Glutathione S-Transferase; Glutathione cursor; Gamma-aminobutyric-acid receptor alpha-6 Subunit S-Transferase 1-6: Glutathione S-Transferase 2: Glutathione precursor; Gamma-aminobutyric-acid receptor rho-1 Subunit S-Transferase 26 Kda; Glutathione S-Transferase Al; Glu Precursor: Gamma-Glutamyl Hydrolase; Ganglioside Gm2 tathione S-Transferase Al-1; Glutathione S-Transferase Activator; Gastrotropin; GDH/6PGL endoplasmic bifunc A3-3; Glutathione S-Transferase Class Pi Chimaera; Glu tional protein precursor Includes: Glucose 1-dehydroge tathione S-Transferase Gita-1A; Glutathione S-Transferase nase; Gdnf Family Receptor Alpha 1: GDP-D-Mannose-4,6- Mu 1. Glutathione S-Transferase Mu 2: Glutathione S-Trans Dehydratase; GDP-Fucose Synthetase; GDP-L-fucose ferase P. Glutathione S-transferase pi; Glutathione S-Trans synthetase; GDP-Mannose 4.6 Dehydratase; GDP-Mannose ferase Tsi-1, Glutathione S-Transferase Ya Chain; Glu 4,6-Dehydratase; GDP-Mannose 6-Dehydrogenase; GDP tathione S-Transferase Yb 1: Glutathione S-Transferase Yfyf: Mannose Mannosyl Hydrolase; General Control Protein Glutathione S-Transferase, Mitochondrial; Glutathione Syn Gcn4; General Secretion Pathway Protein E: General Stress thetase; Glutathione Transferase; Glutathione Transferase; Protein 69; Genome Polyprotein; Gephyrin; Geranyltran Glutathione Transferase Gst 1-3. Glutathione Transferase stransferase; Gfp-Like Chromoprotein Fp595; Gial; Giding Gst1-6: Glutathione Transferase Zeta; Glutathione-Depen Protein-Mglb: Glandular Kallikrein-13; Glcnac1P Uridyl dent Formaldehyde Dehydroge: Glutathione-Dependent transferase Isoform 1: Agx1; Globin; Globin I; Globin Li637; Formaldehyde-Activatin: Glutathione-Requiring Prostaglan Globin-3; Glpe Protein; Glucagon receptor; Glucan 1,3-Beta din D Syntha; Glutathione-S-Transferase; Glyceraldehyde Glucosidase I/II: Glucan 1,4-Alpha-Maltohexaosidase; Glu 3-Phosphate Dehydrogenase; Glyceraldehyde 3-Phosphate carate Dehydratase: Glucoamylase; Glucoamylase-471; Glu Dehydrogenase; Glyceraldehyde 3-Phosphate Dehydroge cocorticoid Receptor, Glucokinase; Glucokinase Isoform 2: nase A; Glyceraldehyde-3-Phosphate Dehydrogenase; Glyc Gluconate 5-Dehydrogenase; Gluconate Kinase; Glu eraldehyde-3-Phosphate Dehydrogenase; Glyceraldehyde-3- cosamine 6-Phosphate Synthase; Glucosamine-6-Phosphate Phosphate Dehydrogenase A: Glyceraldehyde-3-phosphate Deaminase; Glucosamine-6-Phosphate Isomerase: Glu dehydrogenase, liver; Glyceraldehyde-3-phosphate dehydro cosamine-Fructose-6-Phosphate Aminotrans; Glucosamine genase, testis-specific; Glycerol Dehydratase; Glycerol Phosphate N-Acetyltransferase: Glucose 1-Dehydrogenase; Dehydrogenase; Glycerol Kinase; Glycerol Uptake Facilita Glucose 6-Phosphate 1-Dehydrogenase; Glucose 6-Phos tor Protein; Glycerol Uptake Operon Antiterminator-Re: phate 1-Dehydrogenase; Glucose 6-Phosphate Dehydroge Glycerol-3-Phosphate Cytidylyltransferase; Glycerol-3- nase; Glucose Dehydrogenase; Glucose Oxidase; Glucose-1- Phosphate Dehydrogenase; Glycerol-3-phosphate dehydro Phosphatase: Glucose-1-Phosphate Adenylyltransferase genase NAD+, cytoplasmic; Glycinamide ribonucleotide SmaI: Glucose-1-Phosphate Cytidylyltransferase: Glucose formyltransferase (fragment); Glycinamide Ribonucleotide 1-Phosphate Thymidylyltransferas; Glucose-1-Phosphate Transformylase; GLycine alpha 2 receptor, Glycine amidi Thymidylyltransferase: Glucose-6-Phosphate 1-Dehydroge notransferase; Glycine Betaine-Binding Periplasmic Protein; nase; Glucose-6-Phosphate Isomerase: Glucose-Fructose Glycine dehydrogenase; Glycine N-Methyltransferase: Gly Oxidoreductase; Glucose-Fructose Oxidoreductase; Glu cine Oxidase; Glycine receptor alpha-1 chain Precursor: cose-Resistance Amylase Regulator, Glucosylceramidase; Glycine receptor alpha-3 chain; Glycine receptor beta chain; Glucuronyltransferase I: Glutaconyl-Coa Decarboxylase A Glycogen phosphorylase; Glycogen Phosphorylase b: Gly Subunit; Glutamate NMDA receptor subunit epsilon 1 pre cogen Phosphorylase, Liver Form; Glycogen phosphorylase, cursor; Glutamate NMDA receptor subunit epsilon 2 pre muscle form; Glycogen Synthase 1: Glycogen Synthase cursor; Glutamate NMDA receptor subunit epsilon 3 pre Kinase-3 Beta; Glycogenin-1; Glycolate Oxidase; Glycolipid cursor; Glutamate Carboxypeptidase II: Glutamate 2-Alpha-Mannosyltransferase: Glycolipid Transfer Protein; decarboxylase 1: Glutamate decarboxylase 2: Glutamate Glycoprotein D: Glycoprotein-Fucosylgalactoside Alpha Decarboxylase Alpha; Glutamate Decarboxylase Beta; Galac; Glycoprotein-Fucosylgalactoside Alpha-N-Ace; Gly Glutamate Dehydrogenase; Glutamate Dehydrogenase; cosyl Transferase: Glycosylase; Glycosyltransferase A: Gly Glutamate Dehydrogenase 1: Glutamate dehydrogenase 1, cosyltransferase B; Glycosyltransferase Gtfa; mitochondrial precursor; Glutamate dehydrogenase 2, mito Glycosyltransferase Gitfl; Glyoxalase Family Protein; Gly chondrial precursor, Glutamate Racemase; Glutamate recep oxalase II: Glyoxylate reductase/hydroxypyruvate reductase; tor 1 Precursor: Glutamate Receptor 2: Glutamate Receptor Gmp Reductase I: GMP synthase glutamine-hydrolyzing: 2 Precursor; Glutamate receptor 3: Glutamate receptor 4: Gmp Synthetase; Gomesin; Gonadotropin-releasing hor Glutamate Receptor 6: Glutamate Receptor Subunit 2: mone II receptor; Gonadotropin-releasing hormone receptor; Glutamate Receptor, Ionotropic Kainate 1 Glutamate recep GP41 envelope protein (first heptad repeat); Gp70; GPIIb tor, ionotropic kainate 1 precursor; Glutamate Receptor, Receptor; GPIIIa Receptor; Gramicidin; Gramicidin A; Ionotropic Kainate 2: Glutamate receptor, ionotropic kainate Gramicidin B; Gramicidin C; Gramicidin D: Gramicidin 3: Glutamate receptor, ionotropic kainate 5: Glutamate Semi Synthetase 1: Granulocyte colony stimulating factor receptor aldehyde Aminotransferase; Glutamate-Cysteine Ligase; (CD114 antigen); Granulocyte-macrophage colony Stimulat Glutamate-cysteine ligase catalytic subunit: Glutamate-cys ing factor receptor (GM-CSF-R-alpha or CSF2R); Granul teine ligase regulatory Subunit; Glutaminase, kidney isoform; ysin; Granzyme B; Green Fluorescent Protein; Green-Fluo Glutaminase, liver isoform; Glutaminase-Asparaginase; rescent Protein; Griffonia Simplicifolia Lectin 4: Group X Glutamine Aminotransferase: Glutamine Phosphoribosylpy Secretory Phospholipase A2: Growth Differentiation Factor rophosphate: Glutamine Phosphoribosylpyrophosphate Ami 5: Growth Factor Receptor-Bound Protein 2: Growth hor dot; Glutamine Receptor 2: Glutamine Synthetase: mone releasing hormone receptor (GRF receptor); Growth US 2008/0220441 A1 Sep. 11, 2008 arrest-specific protein 6: Grp 1: Gst2 Gene Product; GTP Receptor. Histamine N-Methyltransferase: Histidine ammo Cyclohydrolase I: Gtpase-Activating Protein 1: GTP-Bind nia-lyase. Histidine Containing Protein; Histidine decar ing Nuclear Protein Ran: GTP-Binding Protein Ran: GTP boxylase: Histidine Triad Nucleotide-Binding Protein: Histi Binding Protein Rheb; GTP-Binding Protein YptS1; GTP dine triad nucleotide-binding protein 1: Histidinol Binding Protein Ypt7P; GTP-Binding Protein Ysxc: Dehydrogenase. Histidinol Phosphate Aminotransferase: Guanidinoacetate Methyltransferase; Guanidinoacetate Histidinol-Phosphate Aminotransferase: Histidyl-tRNA syn N-Methyltransferase; Guanine Deaminase; Guanine Nucle thetase: Histo-Blood Group Abo System Transferase: His otide Exchange Factor and I; Guanine Nucleotide Exchange tone Acetyltransferase Gcn5; Histone Deacetylase 8: Histone Factor and Integ; Guanine Nucleotide-Binding Protein G: H3; Histone Methyltransferase Dot 1L: Histone-Lysine Guanine Phosphoribosyltransferase; Guanylate Kinase; Gua N-Methyltransferase, H3 Lysin; Hiv 1 Gp41 Hser Analogue nyl-Specific Ribonuclease T1: Guanyl-Specific Ribonu Peptide Ace-Ile-T: Hiv-1 Integrase: Hiv-1 Protease; HIV-1 clease T1 Precursor; Gurmarin; H-. H. Pylorirdx A: H+/K+ Reverse Transcriptase; HIV-2 Protease; Hmg-Coa Reduc ATPase (Proton pump); Ha1; Haematopoetic Cell Kinase; tase; Holliday Junction DNA Helicase Ruvb: Holliday-Junc Haloalkane Dehalogenase; Halohydrin Dehalogenase; tion Resolvase: Holo-; Holo-D-Glyceraldehyde-3-Phosphate Halorhodopsin; Halotolerance Protein Hall 2: Halotolerance Dehydrogen; Homo Sapiens V-Kit Hardy-Zuckerman 4 Protein Hal 3: Hev NS5B Polymerase: Heys Beta3-Cys Ana Feline; Homoprotocatechuate 2,3-Dioxygenase; logue Of Hiv Gp41; Halp; Head Decoration Protein: Heat Homoserine Dehydrogenase; Homoserine Kinase; Hormone Shock 70 Kda Protein 1: Heat Shock 90Kda Protein 1, Alpha; Receptor Alpha 1, Thra1; Horseradish Peroxidase C1A: Host Heat Shock Cognate Kda70; Heat Shock Locus U; Heat Factor For Q Beta; Hpha; H-Protein; HpV11 Regulatory Pro Shock Protein 90; Heat Shock Protein Hslu; Heat Shock tein E2: Hst2 Protein: HTH-type transcriptional regulator Protein Hsp90-Alpha; Heat Shock Protein Hsp90-Beta; Heat malT: Htlv-1 Gp21 Ectodomain/Maltose-Binding Prote: Shock Protein Hsp33; Heat Shock Transcription Factor; Heat Human Beta2-Glycoprotein I; Human Cd2; Human Cyto Shock-Like Protein 1: Heat-labile enterotoxin B chain pre chrome P450 CYP2D6; Human Cytochrome P450 CYP3A4; cursor; Heat-Labile Enterotoxin B Subunit; Heat-Shock 70 Human Growth Hormone Receptor; Human Immunodefi Kd Protein; Heat-Shock Cognate 70 Kd Protein: Heavy ciency Virus Type 2: Human keratinocyte growth factor chain; Heavy chain 1 B72.3 (murine); Hemagglutinin Precur receptor; Human Neutrophil Gelatinase: Human Ornithine Sor, Hemagglutinin-Neuraminidase; Hemagglutinin Decarboxylase; Human Procathepsin L. Human Protective Neuraminidase Glycoprotein; Hematopoetic Cell Kinase Protein Human RSV Fusion glycoprotein; Human Sigma Hck; Hematopoietic Prostagladin D Synthase: Heme Oxyge Alcohol Dehydrogenase; Human Sorbitol Dehydrogenase; nase; Heme Oxygenase 1; Heme Oxygenase 2: Heme Oxy Human Thioltransferase: Human Thioredoxin Peroxidase-B; genase-1; Heme Pas Sensor Protein: Heme-Based Aerotactic Hut Operon Positive Regulatory Protein: Hyaluronate Lyase: Transducer Hemat; Heme-Based Methyl-Accepting Chemo Hyaluronate lyase precursor, Hyaluronidase; Hyaluronoglu taxis P: Heme-Based Methyl-Accepting Chemotaxis Prote: cosaminidase: Hybrid; Hybrid Cluster Protein: Hydantoin Heme-Binding Protein A: Hemerythrin; Hemk Protein; ase; Hydrogen peroxide-inducible genes activator; Hydro Hemo: Hemocyanin; Hemocyanin; Hemoglobin: Hemoglo lase; Hydrolase Angiogenin; Hydroxyacid Oxidase 3: bin beta chain; Hemoglobin Gamma Chains; Hemoglobin V: Hydroxyacylglutathione Hydrolase; Hydroxyethylthiazole Hemoglobin-Like Protein Hbn: Hemoglobin-Like Protein Kinase; Hydroxylamine Oxidoreductase; Hydroxylamine Hbo: Hemolytic Lectin Cel-III: Hemolytic Lectin Lsla: Reductase: Hydroxymethylglutaryl-CoA lyase; Hydroxyni Hemopexin; Heparan Sulfate; Heparan Sulfate D-Glu trile Lyase, Hydroxyquinol 1,2-Dioxygenase; Hydroxys cosaminyl 3-O-Sulfotra: Heparan Sulfate N-Deacetylase/N- teroid Sulfotransferase: Hypothetical 22.5 Kda Protein. In Sulfotransfe; Heparin Binding Protein; Heparin Cofactor II; Tub1-Cp; Hypothetical 22.5 Kda Protein. In Tub1-Cpr3 I: Heparin cofactor II precursor; Heparin-Binding Growth Fac Hypothetical 28.8 Kda Protein In Psd1-Sk: Hypothetical 32.1 tor 1; Heparin-binding growth factor 1 precursor; Heparin Kda Protein. In Adha-Rcal I: Hypothetical 65.0 Kda Protein Binding Protein: Hepatitis C Virus Ns5B RNA Polymerase: In Cox 14-C: Hypothetical 65.0 Kda Protein In Cox 14-Cos3; Hepatitis C Virus Ns5B RNA-Dependent RNA Pol; Hepato Hypothetical Abc Transporter ATP-Binding; Hypothetical cyte Growth Factor; Hepatocyte Growth Factor Activator Pre Abc Transporter ATP-Binding Pro; Hypothetical Isochoris cursor; Hepatocyte Growth Factor Receptor; Hepatocyte matase Family Protein: Hypothetical Oxidoreductase Yahf: Growth Factor-Regulated Tyrosine; Hepatocyte Nuclear Fac Hypothetical Oxidoreductase Yiak; Hypothetical Oxi tor 1-Alpha; Hepatocyte Nuclear Factor 4-Alpha; Hepatocyte doreductase Yghd; Hypothetical Protein: Hypothetical Pro Nuclear Factor 4-Gamma; Her-1 Protein; Heroin Esterase; tein Af0103: Hypothetical Protein Af1403; Hypothetical Pro Herpes Thymidine Kinase; Hevamine: Hevamine A: Hevea tein Af1521: Hypothetical Protein Af1796: Hypothetical brasiliensis; Hevein; Hevein: Hexokinase; Hexokinase Type Protein Af2198: Hypothetical Protein Agr L 1239; Hypo I: Hexon Protein: Hexose-1-Phosphate Uridylyltransferase: thetical Protein Alriš027; Hypothetical Protein Apc35924; Hi0065; Hil317; High Affinity Immunoglobulin Epsilon Hypothetical Protein Apc36103: Hypothetical Protein Recepto: High affinity immunoglobulin epsilon receptor Aq 328: Hypothetical Protein Bsu33890: Hypothetical Pro alpha-Subunit precursor, High affinity immunoglobulin epsi tein EgcO68; Hypothetical Protein Fli11149; Hypothetical lon receptor gamma-Subunit precursor, High Affinity Ribose Protein HiO828: Hypothetical Protein Hil388.1: Hypotheti Transport Protein Rbsd; High Mobility Group Protein 1: cal Protein Lech: Hypothetical Protein Mds018: Hypotheti High-Affinity Branched Chain Amino Acid Tran; High-Af cal Protein M1247; Hypothetical Protein PaO094; Hypo finity Branched-Chain Amino Acid Tran; High-affinity thetical Protein Pa2260: Hypothetical Protein Pa3270; cAMP-specific 3',5'-cyclic phosphodiesterase 7A: High-af Hypothetical Protein Pa3967: Hypothetical Protein Pa-Ho: finity cationic amino acid transporter-1; High-affinity choline Hypothetical Protein pH0236: Hypothetical Protein pH0642: transporter 1; High-Molecular-Weight Cytochrome C. Hista Hypothetical Protein pH1313; Hypothetical Protein pH1602; mine H1 Receptor; Histamine H2 Receptor; Histamine H4 Hypothetical Protein pH1897: Hypothetical Protein pH1917: US 2008/0220441 A1 Sep. 11, 2008

Hypothetical Protein Rbstp0775: Hypothetical Protein IFNGR1 and indirectly to IFNGR2); Interferon receptor Rv0793; Hypothetical Protein Rv0819; Hypothetical Protein IFNAR1; Interferon receptor IFNAR2c; Interferon Stimu Rv1170; Hypothetical Protein Rv1347C/Mt1389: Hypotheti lated Gene 20 Kda; Interferon-Beta; Interferon-inducible cal Protein Rv2238C/Mt2298: Hypothetical Protein Rv2991; Gtpase: Interleukin 17F: Interleukin-1 type I receptor (IL Hypothetical Protein Slr1257: Hypothetical Protein Smu. 1RI); Interleukin-11 receptor alpha chain (IL-11 R-alpha); 260; Hypothetical Protein Sso2532: Hypothetical Protein Interleukin-12 Beta Chain; Interleukin-19: Interleukin-2: Ta0175: Hypothetical Protein Tal320: Hypothetical Protein Interleukin-2 receptor alpha chain (IL-2-RA); Interleukin-2 Tm()021: Hypothetical Protein Tm()449; Hypothetical Pro receptor beta chain (IL-2-RB); Interleukin-3 precursor; Inter tein Tm1070; Hypothetical Protein Tm1380: Hypothetical mediate conductance Ca(2+)-activated K(+) channel, hIK1; Protein Tm 1457: Hypothetical Protein Tm 1553: Hypotheti Internalin A: Interphotoreceptor retinoid-binding protein; cal Protein Tm 1643; Hypothetical Protein Tm841; Hypo Intestinal Fatty Acid-Binding Protein; Intramolecular Trans thetical Protein Tt0907: Hypothetical Protein Tt 1426; Hypo Sialidase; Intron-Associated Endonuclease 1: Invasin; Inver thetical Protein Vc1899: Hypothetical Protein Vca0042: tase Inhibitor; Inward rectifier potassium channel 2: Iols Pro Hypothetical Protein Ycdx: Hypothetical Protein Ycfc: tein; Ionotropic Glutamate Receptor 5; Iota Toxin Hypothetical Protein Ydce: Hypothetical Protein Yddu: Component Ia, Iota-Carrageenase; Iron; Iron Binding Protein Hypothetical Protein Yese: Hypothetical Protein Yfdw: Fbpa; Iron-Utilization Periplasmic Protein; Isoasparty1 Hypothetical Protein Ygbm; Hypothetical Protein Yhai; Dipeptidase; Isocitrate Dehydrogenase; Isocitrate Dehydro Hypothetical Protein Yhda: Hypothetical Protein Yhfp: genase; Isocitrate dehydrogenase NADSubunit alpha, mito Hypothetical Protein, Similar To Potassium C. Hypothetical chondrial precursor: Isocitrate dehydrogenase NAD sub Protein, Similar To Strepto: Hypothetical Shikimate 5-Dehy unit beta, mitochondrial precursor, Isocitrate dehydrogenase drogenase-L; Hypothetical Transcriptional Regulator I; NAD subunit gamma, mitochondrial precursor; Isocitrate Hypothetical Transcriptional Regulator In Qa: Hypothetical Dehydrogenase Nadp Cytoplasmic; Isocitrate Lyase; tRNA/Rrna Methyltransferase Hi0: Hypothetical Upfol24 Isoflavone O-Methylransferase: Isolectin B4: Isoleucine Protein Yfilh; Hypothetical Upf) 131 Protein pH0828: Hypo tRNA synthetase; Isoleucyl-tRNA Synthetase; Isoliquiritige thetical Upfo204 Protein Af0625; Hypothetical Zinc-Type nin 2'-O-Methyltransferase: Isomerase: Isopenicillin N Syn Alcohol Dehydrogenase; Hypoxanthine Phosphoribosyl thase; Isopentenyl Diphosphate Delta-Isomerase; transferase: Hypoxanthine-Guanine Phosphoribosyltrans Isopentenyl-Diphosphate Delta-Isomerase: Isovaleryl-Coa fera; Hypoxanthine-Guanine Phosphoribosyltransfera; Dehydrogenase; Ispa/Ispf Bifunctional Enzyme: Iswi Pro hypoxanthine-guanine phosphoribosyltransferase: Hypox tein; Kallikrein; Kallikrein 1: Kallikrein 6: Kanamycin nucle anthine-Guanine-Xanthine Phosphoribosyl: lag-Nucleoside otidyltransferase; Kappa-4 Immunoglobulin; Kata Catalase; Hydrolase; Iclr Transcriptional Regulator, Ig Gamma-1 Kdo-8-Phosphate Synthetase; Kdpg Aldolase; Ketoacyl Chain C Region; Ig Gamma-2A Chain C Region, Ig kappa Reductase; Kex1; Killer Cell Immunoglobulin-Like Recep chain V-III region GOL: IgA2: Igf-1 Receptor Kinase; IGG1; tor 2Ds; Kindling Fluorescent Protein; Kinesin; Kinesin II Purple Acid Phosphatase: II-6 Receptor Alpha Chain; Ileal Heavy Chain; Kinesin Heavy Chain-Like Protein; Kinesin Lipid Binding Protein: Imaginal Disc Growth Factor-2: Imi Motor Ncd; Kinesin-Like Protein Kar3; Kinesin-Like Protein dazole Glycerol Phosphate Dehydratase: Imidazole Glycerol Kifl 1; Kinesin-Like Protein Kifl A: Kinesin-Like Protein Phosphate Synthase Hishf Immunoglobulin Alpha Fc Kif2C; Kinesin-Related Motor Protein Eg5; Kynureninase; Receptor Immunoglobulin Heavy Chain Epsilon-1. Immuno Kynurenine/alpha-aminoadipate aminotransferase mito globulin Lambda Light Chain; Immunoglobulin Lambda chondrial; Kynurenine-Oxoglutarate Transaminase I, L., L-2- Light Chain Dimer, Immunoglobulin Vh Domain; Immuno Haloacid Dehalogenase; L-2-Hydroxyisocaproate Dehydro globulin VI Domain: IMP dehydrogenase: Imp-1 Metallo genase; L-3-Hydroxyacyl Coa Dehydrogenase; L-3- Beta-Lactamase; Indole-3-Glycerol Phosphate Synthase: Hydroxyabyl-Coa Dehydrogenase; L-3-Phosphoserine Indole-3-Glycerol-Phosphate Synthase; Indole-3-Pyruvate Phosphatase; Laccase; Laccase; Laccase 1: Laccase 2: Lac Decarboxylase; Indoleamine 2,3-dioxygenase; Inducible tadherin: Lactaldehyde Reductase; Lactate Dehydrogenase; Nitric Oxide Synthase; Influenza A Subtype N2 Neuramini Lactate Dehydrogenase; Lactoferrin, Lactoferrin; Lactose dase; Influenza A Subtype N9 Neuraminidase; Influenza Permease; Lactotransferrin; Lactoylglutathione Lyase; Virus B/Lee/40 Neuraminidase; Inorganic Polyphosphate/ L-Alanine Dehydrogenase; L-Allo-Threonine Aldolase; ATP-Glucomannokinase; Inorganic Polyphosphate/ATP Lambda Exonuclease; Laminarinase 16A: L-Amino Acid Nad Kinase; Inorganic Pyrophosphatase; Inosine Monophos Oxidase; Lanosterol Synthase; Lantibiotic Mersacidin; phate Dehydrogenase 2: Inosine Monophosphate L-Arabinose-Binding Protein: L-Arabinose-Binding Protein Dehydrogenase I: Inosine-5'-Monophosphate Dehydroge Complex With L-A; Large T Antigen; L-Arginine: Glycine nase; Inosine-5'-Monophosphate Dehydrogenase 2: Inosine Amidinotransferase; L-Arginine: Glycine Amidinotrans Adenosine-Guanosine Preferring Nucle; Inosine-Adenosine ferase; L-Asparaginase; L-Asparagine Amidohydrolase; Guanosine-Preferring Nucle; Inositol 1,3,4-Trisphosphate L-Aspartate Ammonia-Lyase; L-Aspartate Oxidase; Lck 5/6-Kinase; Inositol 1,4,5-Trisphosphate Receptor Type 1: Kinase; L-Cysteine/L-Cystine C-S Lyase; Lectin; Lectin; Inositol Monophosphatase; Inositol-3-Phosphate Synthase: Lectin Cel-1, N-Acetyl-D-Galactosamine-Speci; Lectin Inositol-3-Phosphate Synthase; Inositol-Trisphosphate 3-Ki Complex With Lactose; Lectin Pal; Lectin, Isoform 1: Lectin nase A, Insecticyanin A Form: Insulin; Insulin receptor, Insu D2: Leghemoglobin: Leghemoglobin A; Lens Fiber Major lin-Like Growth Factor I; Insulin-Like Growth Factor Recep Intrinsic Protein; Lethal; Lethal Factor; Leucine Aminopep tor 1: Intact Lactose Operon Repressor With Gratuit; tidase; Leucine carboxyl methyltransferase 1: Leucine car Integrase; Integrin alpha-4: Integrin Alpha-L; Integrin Beta-4 boxylmethyltransferase 2: Leucoagglutinating Phytohemag Subunit; Intercellular Adhesion Molecule-1, Intercellular glutinin; Leucoanthocyanidin Dioxygenase; Leucyl-tRNA Adhesion Molecule-2; Interferon gamma receptor including Synthetase; Leucyl-tRNA synthetase, cytoplasmic; Leukoag IFNGR1 and IFNGR2 (IFN-gamma binds directly to glutinin; Leukocidin F Subunit; Leukocyte Elastase; Leuko US 2008/0220441 A1 Sep. 11, 2008 sialin; Leukptriene A-4 Hydrolase; Leukotriene B4 12-Hy C; Mannose-Binding Protein-A; Mannose-Binding Protein droxydehydrogenase/Pros; Levansucrase; Levodione C; Mannosyl-Oligosaccharide 1.2-Alpha-Mannosida; Man Reductase: L-Fucose Isomerase: L-Fuculose 1-Phosphate nosyl-Oligosaccharide Alpha-1,2-Mannosida; Map Kinase Aldolase; L-Fuculose-1-Phosphate Aldolase; L-Histidinol P38; Map Kinase-Activated Protein Kinase 2: Maspin Pre Dehydrogenase; light chain; Light chain 1 B72.3 (murine); cursor, Mast/stem cell growth factor receptor precursor; Lignin Peroxidase; Limonene-1,2-Epoxide Hydrolase; Matrix Gla-protein; Matrix metalloprotease 2 (MMP-2); Lipase; Lipase; Lipase 2: Lipase 3: Lipase, Gastric: Lipid matrix metalloprotease 9 (MMP-9); Matrix Metalloprotein Transfer Protein; Lipi; Lipoate-Protein Ligase, Putative: ase 3: Matrix Metalloproteinase-16; Matrix Metalloprotein Lipoprotein Mxim; Lipoprotein Nlpi; Lipoxygenase-3; ase-2: Matrix Metalloproteinase-8; Matrix Porin; Matrix Lipoyltransferase 1: Lithostathine: Liver Alcohol Dehydro Porin Outer Membrane Protein F; Matrix protein M2: Mdc genase; Liver Carboxylesterase: Liver Carboxylesterase I; Sign1B Type I Isoform: Mdc-Sign2 Type I Isoform; Medium Liver Fatty Acid Binding Protein: Liver Glycogen Phospho Chain Acyl-Coa Dehydrogenase; Melatonin Receptor; Mela rylase; L-Lactate Dehydrogenase; L-Lactate Dehydroge tonin receptor type 1B: Membrane Copper Amine Oxidase; nase; L-lactate dehydrogenase A chain; L-lactate dehydroge Menb: Merozoite Surface Protein-1; Meso-Diaminopimelate nase A-like 6A: L-lactate dehydrogenase A-like 6B; L-lactate D-Dehydrogenase; Metabotropic glutamate receptor 1; dehydrogenase B chain; L-Lactate Dehydrogenase B Chain; Metabotropic Glutamate Receptor Subtype 1; Meta-Cleav L-lactate dehydrogenase C chain; L-Lactate Dehydrogenase age Product Hydrolase; Metallo Beta-Lactamase II; Metal H Chain; L-Lactate Dehydrogenase M Chain; L-Lactate/ lochaperone Atx1; Methionine adenosyltransferase: Malate Dehydrogenase; Lmaj004.091Aaa; Lmaj004144Aaa Methionine Aminopeptidase; Methionine Aminopeptidase 2: Protein; Long-Chain Fatty Acid Transport Protein; Long Methionine Gamma-Lyase; Methionine Synthase; Methion chain-fatty-acid-CoA ligase 1: Long-chain-fatty-acid-CoA ine synthase reductase; Methionine-R-sulfoxide reductase: ligase 3; Long-chain-fatty-acid-CoA ligase 4: Long-Chain Methionine-R-sulfoxide reductase B2: Methionyl Ami Fatty-Acid-CoaSynthetase; Low density lipoproteins (LDL): nopeptidase; Methionyl-tRNA synthetase; Methoxy Mycolic Low-affinity cationic amino acid transporter-2: Low-Density Acid Synthase 2: Methuselah Ectodomain; Methyl-Accept Lipoprotein Receptor, Lc.2: L-Rhamnose Isomerase; ing Chemotaxis Protein; Methylaspartate Mutase S Chain; L-serine dehydratase; L-Sulfolactate Dehydrogenase; Methylated-DNA-protein-cysteine methyltransferase: Meth L-Threonine-O-3-Phosphate Decarboxylase; L-type amino ylcrotonoyl-CoA: Methylcrotonoyl-CoA 2; Methylene Tet acid transporter 1 (LAT1); L-type amino acid transporter 2; rahydromethanopterin Dehydrogen; Methylenetetrahydro Luciferase; Lumazine Synthase; Luteinizing Hormone folate Dehydrogenase/Cy; Methylenetetrahydrofolate Releasing Hormone (LHRH) Receptor; L-Xylulose Reduc reductase; Methylglyoxal Synthase; Methylmalonate-semi tase; Lymphocyte function-associated antigen 1 (CD11a anti aldehyde dehydrogenase; Methylmalonic aciduria protein; gen); Lysine Biosynthesis Enzyme; Lysine hydroxylase; Methylmalonyl Coa Decarboxylase; Methylmalonyl-Coa Lysozyme: Lysozyme C; Lysozyme Insertion Mutant With Carboxyltransferase 12S Su: Methylmalonyl-CoA mutase, Ala Inserted; Lysozyme: Lysozyme Mutant With Cys 54 mitochondrial precursor: Mevalonate Kinase; Mgp-40; Mhc Replaced By Thr. Lysyl Oxidase; Lysyl Oxidase; Lysyl Class I Homolog Mic-A; Microcystin-Lr: microsomal trig tRNA synthetase; Lytic Murein Transglycosylase B; lyceride transfer protein; Microtubule Motor Protein Ncd; M=4=Lactate Dehydrogenase; M1 muscarinic acetylcholine Mimochrome IV. Miniaturized Metalloprotei; Mineralocor receptor; M2 muscarinic acetylcholine receptor; Mac-2 Bind ticoid Receptor; Minor Core Protein Lambda 3: Mitchondrial ing Protein; Macromomycin; Macrophage Metalloelastase; carnitine/acylcarnitine carrier protein CACL; Mitochondrial Macrophage Migration Inhibitory Factor; Magnesium-De Aconitase; Mitochondrial Aldehyde Dehydrogenase; Mito pendent Phosphatase-1; Major Allergen I Polypeptide, Fused chondrial aspartate-glutamate carrier protein; Mitochondrial Chain 2.; Major Autolysin; Major Capsid Protein; Major carnitine/acylcarnitine carrier protein; Mitochondrial folate Envelope Protein E: Major Nad; Major Pollen Allergen BetV transporter/carrier; Mitochondrial glutamate carrier 1; Mito 1-L; Major Urinary Protein; Major Urinary Protein 2: Major chondrial glutamate carrier 2: Mitochondrial ornithine trans Urinary Protein I; Malate Dehydrogenase; Malate Dehydro porter 1; Mitochondrial ornithine transporter 2: Mitogen genase; Malate dehydrogenase, cytoplasmic; Malate Dehy Activated Protein Kinase 10; Mitogen-Activated Protein drogenase, Glyoxysomal; Malate dehydrogenase, mitochon Kinase 14; Moad Related Protein; Modification Methylase drial precursor; Malate Synthase G. Male-B363; Malic Hhai; Modification Methylase Rsri; Module-Substituted Chi Enzyme: Malic Enzyme 2: Malonamidase E2: Malonyl Coa: mera Hemoglobin Beta-A; Mol Id: 1; Molecule: 6-Phospho Acyl Carrier Protein Malonyltra; Maltodextrin Glycosyl Beta-Glucosid: Mol Id: 1; Molecule: Adenylate Kinase; transferase; Maltodextrin Phosphorylase; Maltodextrin Chain; Mol Id: 1; Molecule: Bacteriorhodopsin; Mol Id: 1; Binding Protein; Maltodextrin-Binding Protein Male-B133; Molecule: Beta-Lactamase II: Syno; Mol Id: 1; Molecule: Maltogenic Amylase; Maltooligosyl Trehalose Synthase: Carbamate Kinase-Like C; Mol Id: 1; Molecule: Cyto Maltooligosyltrehalose Trehalohydrolase; Maltoporin; Mal chrome C2; Chain: A Mol Id: 1; Molecule: Endo-1,4-Beta tose Binding Protein Fused With Designed; Maltose Trans Xylanase; Mol Id: 1; Molecule: Glutaredoxin; Engineered; port Protein Malk; Maltose-6'-Phosphate Glucosidase; Mal Mol Id: 1; Molecule: Maltodextrin Phosphoryl; Mol Id: 1: tose-Binding Periplasmic Protein; Maltose-Binding Protein; Molecule: Progesterone Receptor, Molecule: Apomyoglo Maltose-Binding Protein Mutant Male31; Maltotetraose bin; Other Details: Cryst; Molecule: Cathepsin B; Ec: 3.4. Forming Amylase; Mandelate Racemase; Manganese Peroxi 22.1; Mutatio; Molecule: Human ADP-Ribosylation Factor dase; Manganese-Dependent Inorganic Pyrophosphatas; 1; S: Molecule: Protein Kinase C Delta Type; Domain; Mannan Endo-1,4-Beta-Mannosidase; Mannanase A. Man Molybdenum Cofactor Biosynthesis Protein; Molybdenum nitol Dehydrogenase; Mannose Receptor; Mannose-6-Phos Cofactor Biosynthesis Protein A; Molybdopterin Biosynthe phate Isomerase; Mannose-Binding Protein A: Mannose sis Cnx1; Molybdopterin Converting Factor Subunit 2: Binding Protein Associated Serin; Mannose-Binding Protein Molybdopterin-Guanine Dinucleotide Biosynthe: Momor US 2008/0220441 A1 Sep. 11, 2008 din; Mono-ADP-Ribosyltransferase C3; Monoamine oxidase kDa subunit, mitochondrial precursor, NADH-ubiquinone A (MAO-A); Monoamine oxidase B (MAO-B); Monocar oxidoreductase 39 kDa subunit, mitochondrial precursor: boxylate transporter 1; Monocarboxylate transporter 2: NADH-ubiquinone oxidoreductase 42 kDa subunit, mito Monocarboxylate transporter 3: Monocarboxylate trans chondrial precursor, NADH-ubiquinone oxidoreductase 49 porter 4: Monocarboxylate transporter 5; Monocarboxylate kDa subunit, mitochondrial precursor, NADH-ubiquinone transporter 6: Monocarboxylate transporter 7: Monocarboxy oxidoreductase 51 kDa subunit, mitochondrial precursor: late transporter 8: Monocyte Chemotactic Protein 2: Mono NADH-ubiquinone oxidoreductase 75 kDa subunit, mito cyte Differentiation Antigen Cd14; Mono-Heme C-Type chondrial precursor, NADH-ubiquinone oxidoreductase 9 Cytochrome Scya; Monomer Hemoglobin Component III; kDa subunit, mitochondrial precursor, NADH-ubiquinone Monomer Hemoglobin Component IV: Monomeric Sar oxidoreductase AGGG subunit, mitochondrial precursor: cosine Oxidase; Monomethylamine Methyltransferase NADH-ubiquinone oxidoreductase ASHI subunit, mitochon Mtmb 1: Morphinone Reductase: Motuporin; M-Phase drial precursor, NADH-ubiquinone oxidoreductase B12 sub Inducer Phosphatase 2: Mre 11 Nuclease; Mrna Capping unit; NADH-ubiquinone oxidoreductase B14 subunit; Enzyme; Mrna Decapping Enzyme; Mrsd Protein; Mta/Sah NADH-ubiquinone oxidoreductase B15 subunit; NADH Nucleosidase; Mu Class Glutathione S-Transferase Of ubiquinone oxidoreductase B16.6 subunit; NADH Isoenz; Mu Class Tetradeca-; Mu-Conotoxin Piiia; ubiquinone oxidoreductase B17 subunit: NADH-ubiquinone Mu-Conotoxin Smilia; Mucosal Addressin Cell Adhesion oxidoreductase B18 subunit; NADH-ubiquinone oxi Molecule-1; Mu-crystallin homolog; Multidrug Resistance doreductase B22 subunit; NADH-ubiquinone oxidoreductase Abc Transporter ATP-Bin: Multidrug Resistance Protein; B8 subunit; NADH-ubiquinone oxidoreductase B9 subunit; Multidrug Resistance Protein Mexa; Multidrug-Efflux Trans NADH-ubiquinone oxidoreductase chain 1: NADH porter 1 Regulator Bmr; Multiple Antibiotic Resistance Pro ubiquinone oxidoreductase chain 2: NADH-ubiquinone oxi tein Marr; Multiple T-cell antigens (CD1, CD2, CD3, CD5, doreductase chain 3: NADH-ubiquinone oxidoreductase CD5, CD7. CD8); multivitamin transporter; Muscarinic ace chain 4: NADH-ubiquinone oxidoreductase chain 4L: tylcholine receptor M3; Muscarinic acetylcholine receptor NADH-ubiquinone oxidoreductase chain 5; NADH M4; Muscarinic acetylcholine receptor M5; Mutator Mutt ubiquinone oxidoreductase chain 6: NADH-ubiquinone oxi Protein; Muth; Mycolic Acid Synthase: Myoglobin: Myohe doreductase KFYI subunit, mitochondrial precursor, NADH merythrin: Myo-Inositol Hexaphosphate Phosphohydrol; ubiquinone oxidoreductase MLRQ subunit; NADH Myo-Inositol Hexaphosphate Phosphohydrolase; Myo ubiquinone oxidoreductase MLRQ subunit homolog: Inositol Monophosphatase: Myo-Inositol-1-Phosphate Syn NADH-ubiquinone oxidoreductase MNLL subunit: NADH thase: Myo-Inositol-1-Phosphate Synthase; Myo-Inositol-1- ubiquinone oxidoreductase MWFE subunit: NADH Phosphate Synthase-Related Pr; Myosin: Myosin Ie Heavy ubiquinone oxidoreductase PDSW subunit; NADH Chain; Myosin II Heavy Chain; Myosin II Heavy Chain ubiquinone oxidoreductase SGDH subunit, mitochondrial Fused To Alpha-Actini; Myosin-3 Isoform; Myristoyl-Coa: precursor, NADH-ubiquinone oxidoreductase subunit B14. Protein N-Myristoyltransferas; Myrosinase; N Utilization 5a; NADH-ubiquinone oxidoreductase subunit B14.5b: Substance Protein B Homolog: N,N-Dimethylglycine Oxi NADH-ubiquinone oxidoreductase subunit B14.7; NADH dase; N-4 Cytosine-Specific Methyltransferase Pvu; N5-Car ubiquinone oxidoreductase subunit B17.2: Nadp: Nadp boxyaminoimidazole Ribonucleotide Synt; Na"/K+/2Cl- co Dependent Non Phosphorylating Glycerald; Nadp-Depen transporter, N-Acetylgalactosamine-4-Sulfatase; dent Alcohol Dehydrogenase; NADP-dependent malic N-Acetylglucosamine-1-Phosphate Uridyltransf: N-Acetyl enzyme; NADP-dependent malic enzyme, mitochondrial glucosamine-6-Phosphate Deacetylase; N-Acetyllac precursor; Nadp-Dependent Mannitol Dehydrogenase; tosaminide Alpha-1,3-Galactosylt; N-Acetylactosaminide Nadp-Dependent Nonphosphorylating Glyceralde; Nadph Alpha-1,3-Galactosyltr; N-Acetyl-L-Ornithine Carbamoyl Dehydrogenase 1: Nadph Dependent Thioredoxin Reduc transferase; N-Acetylneuraminate Lyase; N-Acetylneurami tase; Nadph\: Ferredoxin Oxidoreductase; Nadph-Cyto nate Lyase Subunit; N-Acylamino Acid Racemase: N-acyl chrome P450 Reductase; Nadph-Flavin Oxidoreductase: glucosamine 2-epimerase; Nad; NAD(P) transhydrogenase, Nadp-Malate Dehydrogenase; Nagd Protein, Putative; Nalp: mitochondrial precursor; Nad-Dependent Alcohol Dehydro Namn Adenylyltransferase: Nbla; N-Carbamyl-D-Amino genase; Nad-Dependent Deacetylase 2; Nad-Dependent For Acid Amidohydrolase; Ndx1; Nei Endonuclease Viii-Like 1: mate Dehydrogenase; Nad-Dependent Malic Enzyme: Nad Neocarzinostatin; Neopullulanase; Neopullulanase 2: Dependent Malic Enzyme: Nad-Dependent Malic Enzyme, Neprilysin; N-Ethylmaleimide Sensitive Fusion Protein; Mitochondria; NAD-dependent malic enzyme, mitochon Neural Globin: Neural Hemoglobin; Neural Kinase, drial precursor; Nadh Oxidase; Nadh Oxidase/Nitrite Reduc Nuk=Eph/Elk/Eck Family Recept; Neuraminidase; tase; Nadh Peroxidase; Nadh Pyrophosphatase; Nadh-Azore Neuraminidase; Neuraminidase N2; Neuraminidase N9; ductase, Fmn-Dependent: NADH-cytochrome b5 reductase: Neuroglobin; Neuronal Calcium Sensor 1: Neuropeptide Y: Nadh-Dependent Butanol Dehydrogenase; NADH Neuropsin; Neurotensin receptor type 2: Neurotoxin Bmk ubiquinone oxidoreductase 13 kDa-A subunit, mitochondrial M4; Neurotoxin Bmk37; Neutral amino acid transporter A: precursor, NADH-ubiquinone oxidoreductase 13 kDa-B sub Neutral amino acid transporter B: Neutral Protease II; Neu unit; NADH-ubiquinone oxidoreductase 15 kDa subunit; trophil Collagenase; Neutrophil elastase; Neutrophil Gelati NADH-ubiquinone oxidoreductase 18 kDa subunit, mito nase; Neutrophil Gelatinase-Associated Lipocalin; Neutro chondrial precursor, NADH-ubiquinone oxidoreductase 19 phil-Activating Protein A; NG.NG-dimethylarginine kDa subunit; NADH-ubiquinone oxidoreductase 20 kDa sub dimethylaminohydrolase 1: NG.NG-dimethylarginine dim unit, mitochondrial precursor, NADH-ubiquinone oxi ethylaminohydrolase 2: Nh; Niacin receptor HM74A: Nickel doreductase 23 kDa subunit, mitochondrial precursor: Responsive Regulator; Nicotinamide Mononucleotide Ade NADH-ubiquinone oxidoreductase 24 kDa subunit, mito nylyl Tra; Nicotinamide Mononucleotide Adenylyl Transfe; chondrial precursor, NADH-ubiquinone oxidoreductase 30 Nicotinamide Mononucleotide Adenylyltransfer; Nicotina US 2008/0220441 A1 Sep. 11, 2008 mide Mononucleotide Adenylyltransfer; Nicotinamide benzoate Synthase: Outer Membrane Lipoprotein Lolb: Nucleotide Transhydrogenase; Nicotinamide Nucleotide Outer Membrane Phospholipase A: Outer Membrane Protein Transhydrogenase; Nicotinamide Nucleotide Transhydroge A: Outer Membrane Protein F: Outer Membrane Protein nase, Su; Nicotinamide-Nucleotide Adenylyltransferase: Nspa: Outer Membrane Protein Tolc; Outer Membrane Pro Nicotinate D-ribonucleotide phyrophsopate phosphoribosyl tein X: Outer Protein Yopm: Ovalbumin; Ovocleidin; Ovo transferase; Nicotinate Mononucleotide: 5,6-Dimethylbenzi; mucoid: Ovotransferrin; Ovotransferrin: Oxygen-insensitive Nicotinate N-methyltransferase: Nicotinate Phosphoribosyl Nad: Oxygen-insensitive NAD(P)H nitroreductase; Oxygen transferase; Nicotinate Phosphoribosyltransferase From Th; Insensitive Nadph Nitroreductase; Oxysterols Receptor LXr Nicotinate-Nucleotide Adenylyltransferase; Nicotinate Beta: Oxytocin receptor (Neurophysin 1); P protein In Nucleotide-Dimethylbenzimidazole; nicotinic acetylcholine cludes: DNA-directed DNA polymerase: P protein Includes: (ganglion) receptor, Nicotinic acetylcholine Receptor DNA-directed DNA polymerase, RNA-directed DNA poly alpha2/alpha3; Nima-Related Protein; Nine-Haem Cyto merase, Ribonuclease H; P/neurokinin 1 Receptor; P1 chrome C; Nine-Heme Cytochrome C; Nit-Fragile Histidine Nuclease; P2 Myelin Protein; P2 Protein; P2Y 12 platelet Triad Fusion Protein; Nitrate Reductase; Nitric Oxide Reduc ADP Receptor; P-30 Protein; P300/Cbp Associating Factor; tase; Nitric Oxide Synthase: Nitric oxide synthase IIB: Nitric P35; P450 Epoxidase; P450 Monooxygenase; P450Cin: Oxide Synthase, Inducible; Nitric-Oxide Reductase Cyto P64K; P97; Palmitoyl Protein Thioesterase 1: Palmitoyl-Pro chrome P450 55A1: Nitric-Oxide Synthase: Nitric-oxide tein Thioesterase 2 Precursor P-Aminobenzoate Synthase synthase brain; Nitric-Oxide Synthase Homolog; Nitric-ox Component I: pancreatic alpha amylase; Pancreatic alpha ide synthase IIC; Nitric-Oxide Synthase, Brain; Nitric-Oxide amylase precursor, Pancreatic Hormone; Pancreatic Lipase Synthase, Endothelial; Nitrite Reductase: Nitrogen Fixation Related Protein 1: Pancreatic Lipase Related Protein 2; pan Regulatory Protein Fixl; Nitrogen Regulation Protein; Nitro creatic triacylglycerol lipase; Pancreatic triacylglycerol gen Regulatorylia Protein; Nitrogen Regulatory Protein Pii; lipase Precursor; Pancreatic Trypsin Inhibitor; Pantoate Nitrogenase Iron Protein; Nitrogenase Iron Protein 1: Nitro Beta-Alanine Ligase; Pantoate-Beta-Alanine Ligase; Pan phorin 1: Nitrophorin 2: Nitrophorin 4: Nitroreductase: tothenate Kinase; Pantothenate Synthetase; Papain; Para Nitroreductase Family Protein; Nitrosocyanin; Nitrous Oxide aminobenzoate synthase component I; Para-aminobenzoic Reductase: Nitrous-Oxide Reductase; Nk Receptor; NMDA acid (PABA); Parathion Hydrolase; Parm; Parvalbumin; Par receptor; N-Methyl-D-Aspartate Receptor Subunit 1: Nimra; valbumin Alpha; Pbcv-1 DNA Ligase; Pcza361.16; P-D- Nogalonic Acid Methyl Ester Cyclase: Non Catalytic Protein Mannopyranosyl Ester), GDP-Mannose 6-Dehydrogenase; 1: Nonaheme Cytochrome C. Non-ATP Dependent L-Selec Pea Lectin: Peanut Lectin: Peanut Peroxidase, Major Cat tive Hydantoina; Non-Catalytic Protein 1: Non-heme chlo ionic Isozym; Pectate Lyase; Pectin Methylesterase; Penicil roperoxidase; Nonspecific Lipid Transfer Protein: Nonspe linV Acylase; Penicillin-binding protein 1A: Penicillin-bind cific Lipid-Transfer Protein: Nonstructural Polyprotein ing protein 1B: Penicillin-binding protein 2: Penicillin Pp 1A: Non-Symbiotic Hemoglobin: Not Applicable: Binding Protein 2A; Penicillin-binding protein 2B: NPC1L1 (Niemann-Pick C1 Like 1) Protein transporter; Penicillin-Binding Protein 2X; Penicillin-binding protein 3: Npqtn Specific Sortase B: Nrdi Protein; NRH dehydrogenase Penicillin-binding protein 4 precursor; Penicillin-Binding quinone 2: Nitpase P4: Nuclear Inclusion Protein A; Nuclear Protein 5: Penicillin-binding protein 5 precursor; Penicillin receptor OB 1: Nuclear Receptor Ror-Alpha; Nucleoside binding proteins 1A/1B: Penicillin-Insensitive Murein 2-Deoxyribosyltransferase: Nucleoside Diphosphate Kinase; Endopeptidase; Penicillopepsin; Pentaerythritol Tetranitrate Nucleoside Diphosphate Kinase A. Nucleoside Diphosphate Reductase; Penton Protein; Pentosyltransferase; Pepp 1: Pep Kinase II: Nucleoside Diphosphate Kinase, Cytosolic; taibol: Peptide: Peptide Amidase; Peptide Deformylase; Pep Nucleoside Diphosphate Transferase: Nucleoside-Specific tide Deformylase 2: Peptide Deformylase Defb; Peptide Channel-Forming Protein; Nudix Homolog: O6-Alkylgua Deformylase Pdfl; Peptide Methionine Sulfoxide Reductase: nine-DNA Alkyltransferase: Obelin; Odorant Binding Pro Peptide N-Myristoyltransferase: Peptide Transporter Tap 1: tein; Odorant Binding Protein Lush; Odorant-Binding Pro Peptide-N: Peptidic Toxin Nodularin: Peptidoglycan Recog tein; Old Yellow Enzyme: Olfactory Marker Protein: nition Protein I-Alph: Peptidoglycan Recognition Protein Sa Oligopeptide Abc Transporter, Periplasmi; Omegac-Txix: Cg 11709; Peptidoglycan synthetase fisl. Peptidyl-Glycine Omp Synthase: Ompk36; Opioid delta Receptor (OP1); Alpha-Amidating Monooxygena; Peptidylglycine Alpha Opioid kappa Receptor (OP2); Opioid mu Receptor (OP3); Hydroxylating Monooxyg: Peptidyl-Lys Metalloendopepti Opioid sigma 1 Receptor; Opioid sigma Receptor (OP4); dase; Peptidyl-Prolyl Cis-Trans Isomerase; Peptidyl-Prolyl Orange Carotenoid Protein; Orc2: Orexin-A.; Orf, Conserved Cis-Trans Isomerase 5: Peptidyl-Prolyl Cis-Trans Isomerase Hypothetical Protein; Orf3; Organic acid transporter 3 A: Pepv: Peridinin-Chlorophyll Protein: Peripheral nerve (OAT3); organic anion transporter (MRP1, MRP2 and Sodium channel 3: Peripheral nerve sodium channel 5; MRP3, MRP4 and MRP5); Organic cation/carnitine trans Peripheral Plasma Membrane Cask: Periplasmic Divalent porter 1; Organic cation/carnitine transporter 2: Organic Cation Tolerance Pr; Periplasmic Divalent Cation Tolerance Hydroperoxide Resistance Protein: Ornithine Aminotrans Protei: Periplasmic Molybdate-Binding Protein: Peroxidase; ferase: Ornithineaminotransferase, mitochondrial; Ornithine Peroxidase C1A: Peroxidase N; Peroxidase/Catalase T: Per Carbamoyltransferase: Ornithine carbamoyltransferase, oxiredoxin; Peroxiredoxin 5 Residues 54-214; Peroxiredoxin mitochondrial; Ornithine Cyclodeaminase; Ornithine Decar 5, mitochondrial precursor; Peroxisomal bifunctional boxylase: Ornithine decarboxylase antizyme: Ornithine enzyme; Peroxisomal Carnitine O-Octanoyltransfer; Peroxi Transcarbamoylase; Orotidine 5'-Monophosphate Decar somal Carnitine O-Octanoyltransferase; Peroxisomal boxylase: Orotidine 5'-Phosphate Decarboxylase; Orotidine Hydratase-Dehydrogenase-Epim; Peroxisomal Hydratase Monophosphate Decarboxylase; Orphan Nuclear Receptor Dehydrogenase-Epimeras; Peroxisomal multifunctional PXr: Osmolarity Sensor Protein; Osmoprotection Protein; enzyme type 2: Peroxisomal Trans 2-Enoyl Coa Reductase: Osmotically Inducible Protein C; Osteocalcin; O-Succinyl Peroxisome Proliferator Activated Receptor A: Peroxisome US 2008/0220441 A1 Sep. 11, 2008

Proliferator Activated Receptor D: Peroxisome Proliferator precursor; Plasmodium proton pump; Platelet Glycoprotein Activated Receptor G; pH 2.5 Acid Phosphatase; Phage T4 Ib Alpha Chain Precurs; Platelet-Activating Factor Acetylhy Lysozyme Insertion Mutant With Ser: Phaseolin; Phenazine drolas; Platelet-Activating Factor Acetylhydrolase; PML Biosynthesis Protein Phzd; Phenazine Biosynthesis Protein RAR Alpha Protein; Pms 1 Protein Homolog 2: Pnp Oxidase; Phzf: Phenazine Biosynthesis Protein Phzg; Phenol 2-Hy Pokeweed Antiviral Protein; Pol Polyprotein; Pollen Allergen droxylase Component B: Phenol 2-Monooxygenase; Phenol Phl P1: Poly; Poly ADP-Ribose Polymerase-1; Polyamine Hydroxylase; Phenylacetone Monooxygenase; Phenylala Oxidase; Polyandrocarpa Lectin; Polygalacturonase; Polyga nine Ammonia-Lyase; Phenylalanine Ammonia-Lyase 1: lacturonase I; Polygalacturonase II; Polygalacturonase Inhib Phenylalanine Hydroxylase; Phenylalanine-4-Hydroxylase; iting Protein; Polynucleotide Kinase; Polyomavirus Coat Phenylalanine-Regulated 3-Deoxy-D-Arabino-H; Phenyla Protein Vp1; Polyomavirus Vp1 Pentamer; Polypeptide lanyl-tRNA synthetase; Phenylalanyl-tRNA synthetase alpha Deformylase; Polypeptide N-Acetylgalactosaminyltrans chain; Phenylalanyl-tRNA synthetase beta chain; Phenyle feras; Polyprotein; Polysialic Acid Capsule Biosynthesis Pro thanolamine N-Methyltransferase; Phenylethylamine Oxi tein; Porcine Alpha-Amylase; Porcine Pancreatic Spas dase; Pheromone Binding Protein; Pheromone-Binding Pro molytic Polypepti; Porin; Porphobilinogen Deaminase; tein; Pheromone-Binding Protein Asp1; Phoq Histidine Porphobilinogen Synthase; Possible 3-Mercaptopyruvate Kinase; Phosphatase; Phosphatase; Phosphate Acetyltrans Sulfurtransf: Possible G-T Mismatches Repair Enzyme: ferase; Phosphate-Binding Protein: Phosphatidylcholine Postsynaptic Density Protein; Postsynaptic Density Protein Transfer Protein: Phosphatidylethanolamine Binding Pro 95; Potassium Channel; Potassium Channel Blocking Toxin tein: Phosphatidylethanolamine-Binding Protein: Phosphati 1; Potassium Channel Protein Rck4; Potassium channel sub dylinositol 3-Kinase Catalytic Subu: Phosphatidylinositol family K member 1: Potassium channel subfamily K member Phosphate Phosphatase; Phosphatidylinositol Transfer Pro 2: Potassium channel subfamily K member 6: Potassium tein Al; Phosphatidylinositol Transfer Protein Alpha; Phos large conductance calcium-activated channel, Subfamily M. phatidylinositol Transfer Protein Sec14P: Phosphatidylinosi alpha member 1: Potassium transporter (bacterial); Potas tol-Specific Phospholipase: Phosphatidylserine sium Voltage-gated channel Subfamily A member 1; Potas decarboxylase proenzyme; Phosphatidylserine receptor; sium Voltage-gated channel Subfamily E member 1; Potas Phospho-2-Dehydro-3-Deoxyheptonate Aldolase; Phospho sium Voltage-gated channel Subfamily H member 2; 2-Dehydro-3-Deoxyheptonate Aldolase.: Phosphocarrier Potassium voltage-gated channel subfamily H member 6: Protein Hpr: Phosphodiesterase 4D: Phosphoenolpyruvate Potassium voltage-gated channel subfamily H member 7; Carboxykinase; Phosphoenolpyruvate Carboxykinase, Potassium voltage-gated channel subfamily KQT member 1: Cytos; Phosphoenolpyruvate Carboxykinase, Cytosolic; Potassium/Sodium Hyperpolarization-Activ; Potassium/So Phosphoenolpyruvate Carboxylase; Phosphoenolpyruvate dium Hyperpolarization-Activated; Potassium-Transporting Mutase; Phosphoenolpyruvate Phosphomutase; Phosphoen Atpase B Chain; Potassium-transporting ATPase beta chain; Zyme Intermediate Of Fru-2,6-Bi; Phosphofructokinase; Pp60V-Src Tyrosine Kinase Transforming Prot; PPAR-alpha; Phosphoglucose Isomerase; Phosphoglycerate kinase; Phos Ppc Decarboxylase Atha13A; Ppca; Ppr; Pr3: Precorrin-6Y phoglycerate kinase 1: Phosphoglycerate kinase, glycoso Methyltransferase/Putative; Precorrin-8X Methylmutase: mal; Phosphoglycerate Mutase; Phosphoglycerate Mutase 1: Precursor Form Of Glucose-Fructose Oxidoredu: Precursor Phosphoglycolate Phosphatase; Phosphoheptose Isomerase: OfPeriplasmic Sugar Receptor; Predicted Amidotransferase: Phosphoinositide-Specific Phospholipase C, I; Phospholi Predicted Cobalamin Binding Protein; Preprotein Translo pase A=2=; Phospholipase A2; Phospholipase A2 Homolog: case Seca; Preprotein Translocase Seca 1 Subunit; Preprotein Phospholipase A2 Homolog 2: Phospholipase A2 inhibitory Translocase Seca Subunit; Prfa; Prion Protein; Probable protein; Phospholipase A2 Isoform 2: Phospholipase A2 Iso 2-Phosphosulfolactate Phosphata; Probable Ammonium form 3: Phospholipase A2, Major Isoenzyme: Phospholipase Transporter; Probable arabinosyltransferase A: Probable ara C; Phospholipase C Delta-1: Phosphomannomutase; Phos binosyltransferase B; Probable arabinosyltransferase C: phomethylpyrimidine Kinase; Phosphonoacetaldehyde Probable Aromatic Acid Decarboxylase; Probable ATP-De Hydrolase; Phosphonoacetate Hydrolase; Phosphopanteth pendent RNA Helicase P47: Probable Butyrate Kinase 2: eine Adenylyltransferase: Phosphoribosyl Anthranilate Probable Cell Division Inhibitor Mind: Probable Cysteine Isomerase: Phosphoribosyl Pyrophosphate Synthetase; Phos Desulfurase: Probable Fosfomycin Resistance Protein; Prob phoribosylamidoimidazole-Succinocar, Phosphoribosy able Glutaminase Ybas; Probable Glutaminase Ybg; Prob lamine-Glycine Ligase; Phosphoribosylformylglycina able Gitpase Engc: Probable GTP-Binding Protein Enga: midine Synth; Phosphoribosylglycinamide Probable Inorganic Polyphosphate/ATP-Nad Kin: Probable Formyltransferase; Phosphoribosyltransferase-Related Pro Inorganic Polyphosphate/ATP-Nad Kin; Probable leucyl tein: Phosphorylated Map Kinase P38-Gamma; Phospho tRNA synthetase, mitochondrial; Probable low molecular serine Aminotransferase; Phosphoserine Phosphatase; Phos weight protein-tyrosine-phosphatase epsP: Probable Malate photriesterase: Phosphotriesterase Homology Protein; Synthase G. Probable Methylisocitrate Lyase; Probable Photoactive Yellow Protein: Photolyase; Phy3 Protein: P-Hy Polysaccharide Deacetylase Pdaa; Probable Pyridoxamine droxybenzoate Hydroxylase; P-Hydroxybenzoate Hydroxy 5'-Phosphate Oxidase; Probable S-Adenosylmethionine: lase Complexed With; P-Hydroxybenzoate Hydroxylase 2-Demethylmen; Probable Serine/Threonine-Protein Kinase; Mutant With Ty; Phytase; Phytochrome Response Regulator Probable Serine/Threonine-Protein Kinase Pel; Probable Rcpa; Phytochrome Response Regulator Rcpb; Phytohemag Serine/Threonine-Protein Kinase Pkn; Probable tautomerase glutinin-L; Pi Glutathione Transferase: Pigment Epithelium ydcE: Probable tyrosyl-tRNA synthetase, mitochondrial; Derived Factor; Pituitary Adenylate Cyclase Activating Po: Probable Uracil Phosphoribosyltransferase: Procarboxypep Placenta Growth Factor; Plasma retinol-binding protein; tidase B; Proclavaminate Amidino Hydrolase; Profilin II; Plasmepsin 2; Plasmepsin II: Plasminogen; Plasminogen Progesterone Receptor; Progesterone Receptor (PR); Pro Activator; Plasminogen Activator Inhibitor-1: Plasminogen gramed Cell Death Protein 8: Programmed Cell Death Pro US 2008/0220441 A1 Sep. 11, 2008 tein 8: Prolactin receptor precursor; Proline Dehydrogenase; glycerate Phospha; Putative Modulator Of DNA Gyrase: Proline Iminopeptidase; Proline oxidase; Proline-tRNA Syn Putative Nadph Dependent Oxidoreductases; Putative thetase; Prolyl Endopeptidase; Prolyl hydroxylase; Prolyl Oxalate Decarboxylase; Putative Oxidoreductase RV2002: Oligopeptidase; Prophospholipase A=2=; Propionyl-CoA Putative Oxidoreductase RV2002: Putative Phosphatase: carboxylase alpha chain; Propionyl-CoA carboxylase beta Putative Polyprotein/Phosphatase; Putative Protease La chain; Propionyl-Coa Carboxylase Complex B Subunit; Homolog: Putative Riboflavin Kinase; Putative Snrnp Sm Prostacyclin synthase; Prostaglandin D2 receptor; Prostag Like Protein: Putative Sugar Kinase; Putative Transcriptional landin E2 receptor, EP1 subtype: Prostaglandin E2 receptor, Regulator; Putative Xylanase; Putidaredoxin Reductase: EP2 subtype: Prostaglandin Endoperoxide H Synthase-1; Putrescine-Binding Protein; Pyelonephritic Adhesin; Pyra Prostaglandin F Synthase; Prostaglandin F2-alpha receptor; nose Oxidase; Pyridoxal kinase; Pyridoxal Phosphate Bio Prostaglandin G/HSynthase 1 Precursor; Prostaglandin G/H synthetic Protein Pdx; Pyridoxal phosphate phosphatase: Synthase 2: Prostaglandin H2 Synthase: Prostaglandin H2 Pyridoxamine Kinase; Pyridoxine 5'-Phosphate Oxidase; Synthase-1; Prostaglandin H2 Synthase-2: Prostaglandin Pyridoxine 5'-Phosphate Oxidase; Pyridoxine 5'-Phosphate Receptor; Prostaglandin-E2 9-Reductase; Prostate-specific Synthase: Pyridoxine-5'-phosphate oxidase; Pyrimidine membrane antigen (7E11-C5.3 antigen/FOLH1-human/ Nucleoside Phosphorylase; Pyrogenic Exotoxin B: Pyro glutamate carboxypeptidase 11); Prostatic Acid Phosphatase; phosphatase: Pyrr Bifunctional Protein; Pyrroline-5-car Protease; Protease II; Protease Retropepsin; Protease Syn boxylate reductase 1: Pyrroline-5-carboxylate reductase 2: thase and Sporulation Negati; Protease Vii; Protegrin 3: Pro Pyrroline-5-carboxylate synthetase; Pyruvate carboxylase; tein: Ketosteroid Isomerase: Protein 1D10; Protein Arginine Pyruvate Decarboxylase; Pyruvate dehydrogenase; Pyruvate Methyltransferase Prmt3; Protein Arginine N-Methyltrans Dehydrogenase E1 Component; Pyruvate dehydrogenase E1 ferase 1: Protein C: Protein Fkbi; Protein Kinase C. Protein component alpha Subunit, Somatic form, mitochondrial pre Kinase C Interacting Protein; Protein Kinase C, Theta Type: cursor, Pyruvate dehydrogenase E1 component alpha Sub Protein Kinase Ck2; Protein Maf: Protein Methyltransferase unit, testis-specific form, mitochondrial precursor, Pyruvate Hemk: Protein Ninb: Protein Rdmb: Protein With Similarity Dehydrogenase Kinase, Isozyme 2: Pyruvate dehydrogenase To Flavin-Contai; Protein Ybgc: Protein Ybhb: Protein Ycei: protein X component, mitochondrial precursor, Pyruvate Protein Yebr; Protein Yesu: Protein Yfbg: Protein Yof Pro Kinase; Pyruvate kinase, isozymes M1/M2; Pyruvate Kinase, teinYtnj; Protein: Igfbp-1Antagonist; Proteinase; Proteinase Isozymes R/L. Pyruvate Oxidase; Pyruvate Phosphate Diki K; Protein-Glutamine Gamma-Glutamyltransferase: Protein nase; Pyruvate, Orthophosphate Dikinase; Pyruvate: ferre Glutamine Glutamyltransferase E.; Protein-glutamine doxin oxidoreductase (PFOR) in anaerobes; Pyruvate-Ferre glutamyltransferase E precursor: Protein-Glutamine doxin Oxidoreductase; Pyruvoyl-Dependent Arginine Glutamyltransferase E3; Protein-L-Isoaspartate; Protein-L- Decarboxylase; Pyst1: Quercetin 2,3-Dioxygenase; Queuine Isoaspartate O-Methyltransferase: Protein-Tyrosine Phos tRNA-Ribosyltransferase: Quinohemoprotein Alcohol phatase 1B: Protein-Tyrosine Phosphatase Yoph: Protein-Ty Dehydrogenase; Quinolinate Phosphoribosyl Transferase: rosine Phosphatase, Non-Recept; Protein-Tyrosine Quinolinic Acid Phosphoribosyltransferase: Quinone Oxi Phosphatase, Non-Receptor T. Protein-Tyrosine-Phos doreductase; Quinone Reductase; Quinone Reductase Type phatase; Prothrombin; Prothrombin; Prothrombin Fragment 2: Quinone-Reductase; Quinoprotein Ethanol Dehydroge 1; Protoheme Ferrolyase; Proton-coupled amino acid trans nase; Rab GDP Disossociation Inhibitor Alpha; Rab6 Gitpase: porter 1: Proto-Oncogene Serine/Threonine-Protein; Proto RAC serine/threonine-protein kinase; Rac-Alpha Serine/ Oncogene Serine/Threonine-Protein Kina; Proto-Oncogene Threonine Kinase; Radixin; RAF proto-oncogene serine/ Tyrosine-Protein Kinase Abl1; Proto-Oncogene Tyrosine threonine-protein kinase; Ramoplanin; Ran; Rap2A; Ras Protein Kinase Lck; Proto-Oncogene Tyrosine-Protein Related C3 Botulinum Toxin Substrate 1 I Ras-Related Kinase S. Proto-Oncogene Tyrosine-Protein Kinase Src.: Pro Protein Rab-1 1A: Ras-Related Protein Rab-5A; Ras-Related tooncoprotein; Protoporphyrinogen Oxidase, Mitochondria; Protein Rab-7: Ras-Related Protein Rab-9A, Ras-Related P-Selectin; PseudoaZurin; Pseudocatalase; Pseudomonas Protein Ral-A: Ras-Related Protein Sec4; Rat ADP-Ribosy Aeruginosa Lectin II: Psychrophilic Phosphatase I; Pteridine lation Factor-1; Rat Synapsin I: Re-Rnase6 Ribonuclease: Reductase; Pteridine Reductase 1; Pteridine Reductase 2; Pts Reca; Reca Protein; Receptor Protein-Tyrosine Kinase System, Chitobiose-Specific lib Comp; Pulmonary Surfac Erbb-3 Receptor-Type Adenylate Cyclase Gresag 4.1; tant-Associated Protein A: Pulmonary Surfactant-Associated Recombinant Lignin Peroxidase H8; Recombination Protein Protein D; Pumilio 1: Pur Operon Repressor; Pure: Purine Recr; Red Fluorescent Protein Fp611; Redox-Sensing Tran Nucleoside Phosphorylase; Purine Regulatory Protein Yabi: scriptional Repressor; Regulatory Protein Blar1; Regulatory Purine Trans Deoxyribosylase; Purine-Nucleoside Phospho Protein Teni; Renal Dipeptidase; Renin; Renin; Replicase, rylase; Purple Acid Phosphatase; Purple Acid Phosphatase: Hydrolase Domain; Replication Protein; Resistin; Response Putative Acyl-Coa Thioester Hydrolase Hi0827; Putative regulator pleD; Restriction Endonuclease Bglii; Reticulon 4 Alkylsulfatase Atsk; Putative Alpha-L-Fucosidase; Putative Receptor; Reticulon 4 Receptor; Retinal dehydrogenase 1: Aspartate Aminotransferase; Putative ATP-Dependent Clp Retinal dehydrogenase 2: Retinal Dehydrogenase Type II; Protease Proteoly; Putative Betaine Aldehyde Dehydroge Retinoic acid induced 3 protein; Retinoic acid receptor alpha; nase; Putative Blue Light Receptor; Putative Cellulase; Puta Retinoic Acid Receptor Beta: Retinoic Acid Receptor tive Cellulase Celé: Putative Clc Family, Chlorine Transport Gamma-1: Retinoic Acid Receptor Gamma-2: Retinoic acid Prot: Putative Cytochrome P450; Putative Cytochrome P450 receptor responder protein 1: Retinoic acid receptor RXR 154A1: Putative Family 31 Glucosidase Yici; Putative Flavin alpha; Retinoic acid receptor RXR-beta; Retinoic acid recep Oxidoreducatase; Putative Glur0 Ligand Binding Core: Puta tor RXR-gamma; Retinoid X Receptor, Beta: Retinol Bind tive GlurO Ligand Binding Core: Putative G-protein coupled ing Protein Complexed With Axero: Retinol Dehydratase: receptor 40; Putative Ketoacyl Reductase; Putative Lipase retinol dehydrogenase 12; retinoldehydrogenase 13; Retinol From The G-D-S-L Family: Putative Mannosyl-3-Phospho binding protein I: Retinol-binding protein 11; Retinol-bind US 2008/0220441 A1 Sep. 11, 2008 ing protein III: Retinol-binding protein IV: Retropepsin; Serine/threonine-protein kinase receptor R3: Serine/Threo Reverse Gyrase; Rifbc; Rfcs; Rhamnogalacturonan Acety nine-Protein Kinase Ymir216C; Serine-Carboxyl Proteinase; lesterase; Rhamnogalacturonase A.; Rhamnulose-1-Phos Serine-pyruvate aminotransferase: Serotonin N-Acetyltrans phate Aldolase; Rhizome Secoisolariciresinol Dehydroge ferase: Serotransferrin; Serotransferrin precursor; Serratia nase; Rhoa; Rhodanese; Rhodopsin; Rho-Related GTP Marcescens Aminoglycoside-3-N-Acet; Serum Albumin; Binding Protein Rhoe: Riboflavin kinase; Riboflavin Kinase/ Serum albumin precursor; Serum Amyloid P Component; Fmn Adenylyltransferase: Riboflavin Synthase: Riboflavin Serum Transferrin; Seryl-tRNA synthetase; Set9; Sex Comb Synthase Alpha Chain; Ribokinase; Ribonuclease; Ribonu On Midleg Cg.9495-Pa; Sex Hormone-Binding Globulin; Sex clease 1: Ribonuclease 4: Ribonuclease A. Ribonuclease Hii; hormone-binding globulin precursor: Sfl 1-Rinase; Sfua; Sh3 Ribonuclease Mc; Ribonuclease Mc1; Ribonuclease Pancre Domain-Binding Glutamic Acid-Rich Protein; Shiga Toxin atic; Ribonuclease pH; Ribonuclease Sa; Ribonuclease T1: B-Chain; Shiga-Like Toxin I B Subunit; Shiga-Like Toxin I Ribonuclease U2: Ribonuclease UK114; Ribonuclease Z: Subunit B: Shiga-Like Toxin lie B Subunit; Shikimate 5'-De Ribonuclease, Seminal; Ribonucleoside-Diphosphate hydrogenase; Shikimate 5-Dehydrogenase; Shikimate 5-De Reductase 2 Alpha; Ribonucleoside-Diphosphate Reductase hydrogenase 2: Shikimate Kinase; Short Chain 3-Hydroxya M2 Chai; Ribonucleotide reductase; Ribonucleotide Reduc cyl-Coa Dehydrogenase; Short chain 3-hydroxyacyl-CoA tase R2: Ribonucleotide Reductase R2-2 Small Subunit; dehydrogenase, mitochondrial precursor; Short Chain Acyl Ribonucleotide Reductase Subunit R2F: Ribose 5-Phosphate Coa Dehydrogenase; Short-Chain Dehydrogenase/Reduc Isomerase: Ribose-5-Phosphate Isomerase A: Ribose-5- tase Family M: Shp-2: Siah-1A Protein; Sialic Acid Binding Phosphate Isomerase Rpib; Ribosomal Protein L1; Riboso Ig-Like Lectin 7: Sialidase; Sialidase 2: Sialoadhesin: Sigfl mal Protein L4; Ribosomal Protein S6 Kinase Alpha 5; Ribo Gfp Fusion Protein; Sigma Factor Sigb Regulation Protein somal Small Subunit Pseudouridine Sy: Ribosomal Small Rsbq; Signal Peptidase I: Signal Processing Protein; Signal Subunit Pseudouridine Syntha; Ribosome Recycling Factor; Processing Protein; Signal Recognition Particle 9/14 Fusion Ribosome-Inactivating Protein Alpha-Trichos; Ribulose-1,5 Prot; Signal Recognition Particle Protein; Signal Sequence Bisphosphate Carboxylase/Oxygen; Ricin; Ricin A Chain; Recognition Protein Ffh; Signalling Protein Spb; Silent Infor Right-Handed Coiled Coil Tetramer; Right-Handed Coiled mation Regulator 2; Simian Immunodeficiency Virus; Simi Coil Trimer; RNA 3’-Terminal Phosphate Cyclase; RNA lar To Synaptotagmini/P65: Similar To Thymidylate Kinase; Dependent RNA Polymerase: RNA Ligase 2: RNA Poly Sindbis Virus Capsid Protein; Single Stranded DNA Binding merase Alpha Subunit; RNA-Binding Protein Regulatory Protein; Siroheme Biosynthesis Protein Met8; Siroheme Subunit; RNA-Dependent RNA Polymerase: RNA-Directed Synthase: Skeletal Dihydropydrine Receptor. Smad3: Small RNA Polymerase: Rnase L Inhibitor; Rnase Ngr3; Rind3/ Inducible Cytokine A20; Small inducible cytokine A23 pre Rhoe Small GTP-Binding Protein; Rod Shape-Determining cursor; Small Inducible Cytokine A5; Small Inducible Cyt Protein Mreb; Rop Ala2Ile2-6; Rubredoxin; Rubredoxin: bkine B10; Small Nuclear Ribonucleoprotein Homolog: Oxygen Oxidoreductase; Ruvb; Rv3303C-Lpda; Ryanodine Small Tetraheme Cytochrome C; Sm-Like Archaeal Protein receptor 1: S-Gamma86-Beta-Mercaptoethanol-Lysozyme; 1: SNAP-25; Sniffer Cg 10964-Pa; Sodium- and chloride S-Gamma97-Beta-Mercaptoethanol Lysozyme: S100A6; dependent creatine transporter 1: Sodium- and chloride-de S3-Rnase; Saccharopepsin; Saccharopepsin precursor, Sac pendent creatine transporter 2: Sodium- and chloride-depen charopine Reductase; S-Adenosylhomocysteine Hydrolase; dent GABA transporter 1: Sodium- and chloride-dependent S-Adenosyl-L-Homocysteine Hydrolase; S-Adenosyl-L- neutral and basic amino acid transporter B(0+); Sodium/Hy Methionnine: Salicylic Acid Car; S-Adenosylmethionine drogen Exchanger 1: Sodium/potassium-transporting Decarboxylase Proen; S-Adenosylmethionine Decarboxy ATPase alpha-1 chain; Sodium/potassium-transporting lase Proenzyme: S-Adenosylmethionine Synthetase; S-Ad ATPase gamma chain; Sodium-dependent norepinephrine re enosyl-Methyltransferase Mraw; Salicylic Acid-Binding uptake pump; Sodium-dependent proline transporter; Protein 2; Salivary Lipocalin; Salivary Nitrophorin; Salvia Sodium-dependent serotonin re-uptake pump; Soluble Cyto officinalis; Sandostatin: Saposin B: Sarl; Sarcoplasmic/En chrome B562; Soluble Lytic Transglycosylase Slt70; Soluble doplasmic Reticulum Calcium A; Sarcosine Oxidase; Sar Quinoprotein Glucose Dehydrogenase; Soluble Tumor cosine Oxide: Scaffolding Dockerin Binding Protein A; Scav Necrosis Factor Receptor 1: Solute carrier family 12, member enger receptor class B member 1; Scorpion Neurotoxin; 2: Solute carrier family 12, member 4: Solute carrier family Scytalone Dehydratase: SDHA protein; Sec 14-Like Protein 12, member 5; Solute carrier family 12, member 6: Solute 2: SEC14-like protein 3: SEC14-like protein 4: Sec18P: carrier family 12, member 7: Solute carrier family 13, mem Secretin receptor; Sedolisin; Seed Coat Peroxidase; Seed ber 1: Solute carrier family 13, member 2: Solute carrier Lipoxygenase-3; Segmentation Polarity Homeobox Protein family 13, member 3: Solute carrier family 23 member 1: Engrai; Segregation Protein; Selenocysteine Lyase; Selenos Solute carrier family 23 member 2: Somatostatin receptor ubtilisin Bpn: Semaphorin 3A. Seminal Plasma Protein Pdc type 1: Somatostatin receptor type 2: Sorbitol Dehydroge 109; Sensor Kinase Cita; Sensor Protein Fixl; Sensory nase; Sorting Nexin Grd 19; sp|O43272|PROD HUMAN Rhodopsin II; Sepiapterin Reductase: Serine Acetyltrans Proline oxidase, mitochondrial precursor (EC 1.5.3.-) (Pro ferase: Serine Carboxypeptidase; Serine Hydroxymethyl line dehydrogenase); sp|P04746|AMYP HUMAN Pancre transferase: Serine hydroxymethyltransferase (mitochon atic alpha-amylase precursor; sp|P04798|CP1A1 HUMAN drial); Serine Hydroxymethyltransferase, Cytosolic: Serine Cytochrome P450 1A1 (EC 1.14.14.1); sp|P05108|C11A palmitoyltransferase 1: Serine palmitoyltransferase 2: Serine HUMAN Cytochrome P450 1A1; sp|P05177|CP12 HU Protease; Serine racemase; Serine/Threonine Kinase 6: MAN Cytochrome P450A2; sp|P05177|CP1A2 HUMAN Serine/Threonine Protein Kinase Tao2; Serine/Threonine Cytochrome P450 1A2 (EC 1.14.14.1); sp|P05181 ICP2E1 Protein Phosphatase 5: Serine/Threonine Protein Phos HUMAN Cytochrome P450 2E1 (EC 1.14.14.1): phatase Pp1-Gam: Serine/threonine-protein kinase sp|P05186|PPBT HUMAN Alkaline phosphatase, tissue ALS2CR7: Serine/threonine-protein kinase receptor R2: nonspecific isozyme precursor; sp|P08263|GSTA 1 HU US 2008/0220441 A1 Sep. 11, 2008 90

MAN Glutathione S-transferase Al; sp|P08684|CP3A4 HU nine Dihydrolase; Succinyl-CoA ligase GDP-forming beta MAN Cytochrome P450 3A4 (EC 1.14.13.67); chain; Sucrose Phosphorylase; Sucrose-Specific Porin: Sugar sp|P09210|GSTA2 HUMAN Glutathione S-transferase A2; Transport Protein; Sulfatase Modifying Factor 2; Sulfate sp|P10632|CP2C8 HUMAN Cytochrome P450 2C8 (EC Adenylyltransferase; Sulfide Dehydrogenase; Sulfite Oxi 1.14.14.1); sp|P10635|CP2D6 HUMAN Cytochrome P450 dase; Sulfite Reductase; Sulfite Reductase Hemoprotein; Sul 2D6 (EC 1.14.14.1); sp|P11509|CP2A6. HUMAN Cyto folipid Biosynthesis; Sulfolipid Biosynthesis Protein Sqd 1: chrome P450 2A6 (EC 1.14.14.1); sp|P11712|CP2C9 HU sulfonyl urea receptor (SUR1); Sulfonylurea receptor 1; Sul MAN Cytochrome P450 2C9 (EC 1.14.13.80); fonylurea receptor 2; Sulfotransferase; Sulfotransferase Fam sp|P15104|GLNA HUMAN Glutamine synthetase (EC 6.3. ily, Cytosolic, 2B, Memb; Sulfurtransferase: Superoxide Dis 1.2) (Glutamate-ammonia ligase) (GS); sp|P15289|ARSA mutase; Superoxide Dismutase Cu-Zn; Superoxide HUMAN Arylsulfatase A precursor (EC 3.1.6.8) (ASA) Dismutase Fe: Superoxide Dismutase Mn). Mitochondrial; (Cerebroside-sulfatase) Contains: Arylsulfatase A compo Superoxide Dismutase Ni: Suppressor Of Tumorigenicity nent B: Arylsulfatase A component C: sp|P15531 INDKA 14: Surface Layer Protein; Surface Protein; Survival Protein HUMAN Nucleoside diphosphate kinase A (EC 2.7.4.6); E: Synapsin Ia: Synthetic Designed Peptide Alpha-1: Syn sp|P16152|DHCA HUMAN Carbonyl reductase NADPH thetic PeptideAnalogue Of Shk Toxin; System Namino acid 1; sp|P16435INCPR HUMAN NADPH-cytochrome P450 transporter 1; T Lymphocyte Activation Antigen; T3-785: T4 reductase; sp|P19099|C11B2 HUMAN Cytochrome P450 Lysozyme; Tachylectin-2, Tagatose-Bisphosphate Aldolase 11B2.: sp|P19971 TYPH HUMAN Thymidine phosphory Agay; Tailspike Protein: Taka Amylase; Tandem pH Domain lase; sp|P20711|DDC HUMAN Aromatic-L-amino-acid Containing Protein-1; Taq DNA Polymerase: Taste receptor decarboxylase; sp|P20813|CP2B6 HUMAN Cytochrome type 1 member 1: Taste receptor type 1 member 2: Taste P450 2B6 (EC 1.14.14.1); sp|P21397|AOFA HUMAN receptor type 1 member 3: Tatd-Related Deoxyribonuclease: Amine oxidase flavin-containing; sp|P22309|UD11 HU Tat-Interacting Protein Tip30; T-Cell Ecto-ADP-Ribosyl MAN UDP-glucuronosyltransferase 1-1 precursor: transferase 2: T-Cell Ecto-ADP-Ribosyltransferase 2; T-cell sp|P223101UD14 HUMAN UDP-glucuronosyltransferase: surface glycoprotein CD3 epsilon chain (CD3E); Tap-Glu sp|P23141|EST1 HUMAN Liver carboxylesterase 1 precur cose-4,6-Dehydratase; Tdp-Glucose-4,6-Dehydratase: sor (EC 3.1.1.1): sp|P27338|AOFB HUMAN Amine oxi Techylectin-5A: Tem-1 Beta Lactamase; Tem-1 Beta-Lacta dase B; sp|P27707|DCK HUMAN Deoxycytidine kinase mase; Terminal Deoxynucleotidyltransferase Short I; Teta (EC 2.7.1.74) (dCK); sp|P28332|ADH6 HUMAN Alcohol nus Toxin; Tetanus Toxin He; Tetanus Toxin Heavy Chain; dehydrogenase 6 (EC 1.1.1.1): sp|P32320CDD HUMAN Tetra-; Tetracycline Repressor; Tetrahydrodipicolinate Cytidine deaminase (EC 3.5.4.5); sp|P33261|CP2CJ HU N-Succinyltransferase; Tetrameric Beta-Beta-Alpha Mini MAN Cytochrome P450 2C19 (EC 1.14.13.80); Protein: Tgf-Beta Receptor Type I: Tgf-Beta Receptor Type sp|P42898 MTHR HUMAN Methylenetetrahydrofolate II: Th10Aox: Th1 OBox: Th1 Ox; Thaumatin I: The GTP reductase; sp|P479891XDH HUMAN Xanthine dehydroge Binding Protein Obg: The Hypothetical Protein; The Major nase/oxidase; sp|P48775 IT23O HUMAN Tryptophan 2,3- Capsid Protein Of Pbcv-1, Vp54: Thermal Hysteresis Pro dioxygenase (EC 1.13.11.11) (Tryptophan pyrrolase) (Tryp tein; Thermolysin; Thermonuclease; Thermonuclease pre tophanase) (Tryptophan Oxygenase) (Tryptamin 2,3- cursor; Thermosome Alpha Subunit; Thiamin Phosphate dioxygenase) (TRPO); sp|P50135|HNMT HUMAN Synthase; Thiamin Pyrophosphokinase; Thiamine pyrophos Histamine N-methyltransferase; sp|Q06278 AD HUMAN phokinase; Thiamine transporter 1: Thiamine triphosphatase; Aldehyde oxidase (EC 1.2.3.1); splQ07973|CP24A HU Thiazide-sensitive sodium-chloride cotransporter; Thiazole MAN Cytochrome P450 24A1; sp|Q16696||CP2AD HU Biosynthetic Enzyme: Thioesterase: Thioesterase I: Thiol MAN Cytochrome P450 2A13 (EC 1.14.14.1): Peroxidase; Thiol: Disulfide Interchange Protein; Thiol-Dis sp|Q6GRKO|Q6GRKO HUMAN Cytochrome P450, sub ulfide Oxidoreductase Resa; Thioredoxin; Thioredoxin family IIIA, polypeptide 4; sp|Q9NTN31S35D11 HUMAN reductase; Thiostrepton; Threonine Synthase: Threonine syn UDP-glucuronic acid; Sperm Whale Metacuomyoglobin thase-like 1: Threonyl-tRNA Synthetase: Threonyl-tRNA Variant H93G: Spermidine Synthase; Spermidine/Pu Synthetase 1: Thrombomodulin; Thrombospondin 1: Throm trescine-Binding Protein; Spermine oxidase; Sphingosine-1- boxane A2 receptor; Thromboxane A2 synthase; Thrombox phosphate lyase 1: Split-Soret Cytochrome C; Spo0A: ane synthase; Thymidine Kinase; Thymidine Kinase, Cyto SpoOB-Associated GTP-Binding Protein; Spore Coat solic: Thymidine Phosphorylase; Thymidylate Kinase; Polysaccharide Biosynthesis Prote: Spp-40; Squalene Epoxi Thymidylate Synthase; Thymidylate Synthase Thyx; Thy dase; Squalene-Hopene Cyclase, Squalene-Hopene Cyclase; roid hormone receptor alpha; Thyroid Hormone Receptor Sr Protein Kinase; S-Ribosylhomocysteinase; Sst 1-Selective Beta-1; Thyroid hormone receptor beta-2; Thyroid peroxi Somatosatin: Sst 1-Selective Somatosatin Analog: Stapho dase; Thyrotropin receptor (Thyroid stimulating hormone pain; Staphylococcal Enterotoxin B: Stat Protein; Stem/Leaf receptor); Thyroxine-binding globulin precursor; Tick-Borne Lectin Db58; Steroid Delta-Isomerase; Steroid Sulphotrans Encephalitis Virus Glycoprotein; Tissue-Type Plasminogen ferase: Sterol 14-alpha demethylase; Sterol Carrier Protein 2: Activator; Toho-1 Beta-Lactamase; Toll-Like Receptor 2: Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylat Toll-like receptor 7 precursor; Toluene-4-Monooxygenase ing; Steryl-Sulfatase: Sticholysin II: Streptavidin; Streptavi System. Protein C; Topoisomerase IV subunit A: Topoi din precursor; Streptogramin A Acetyltransferase; Stringent somerase IV Subunit B: Tora Specific Chaperone; Toxin Starvation Protein A; Stromelysin 3: Stromelysin-1; Struc Bmkk4; tr|Q17328|Q17328. CAEEL Avermectin-sensitive tural Polyprotein; Subtilisin 8321; Subtilisin 8324; Subtilisin glutamate-gated chloride channel GlucI beta; Bpn"; Subtilisin BPN' 8350; Subtilisin Carlsberg: Subtilisin tr|Q46759|Q46759 ECOLI Beta-lactamase; Carlsberg, Type Viii; Subtilisin PbS2; Subtilisin-Carlsberg; tr|Q5VUYOIQ5VUYO HUMAN Novel protein similar to Subunit C. Succinate dehydrogenase; Succinate semialde esterases; tr|Q75NA5|Q75NA5-MUSDO GABA-gated chlo hyde dehydrogenase, mitochondrial precursor, Succinylargi ride channel subunit; tr|Q8ITG2|Q8ITG2-CAEEL GABA-A US 2008/0220441 A1 Sep. 11, 2008 receptor subunit; Trafficking Protein Particle Complex Sub Synthetase: Tyrosyl-tRNA synthetase, cytoplasmic; U1A unit; Trai Protein; Transaldolase; Transcarboxylase 5S Sub RNA Binding Domain; Ubiquinol-cytochrome-c reductase unit; Transcobalamin I; Transcobalamin II; Transcription complex core protein I, mitochondrial precursor, Ubiquitin; Antitermination Protein Nusg: Transcription Antiterminator Ubiquitin-Activating Enzyme E1 1, Ubiquitin-Conjugating Lict; Transcription factor PPAR gamma; Transcriptional Enzyme E2 2: Ubiquitin-Conjugating Enzyme E2-25 Kda; Activator Tena; Transcriptional Regulator; Transcriptional Ubiquitin-Like Protein 7, Rub 1: Ubiquitin-Protein Ligase E3 Regulator Nadr: Transcriptional Regulator, Hth 3 Family; Mdm2; Udp-3-O-3-Hydroxymyristoyl N-Acetylglucosa; Transcriptional Regulator, Rok Family; Transcriptional Udp-Galactopyranose Mutase; Udp-Galactose 4-Epimerase; Regulatory Protein Fixi: Transcriptional Regulatory Protein, Udp-Galactose 4-Epimerase; Udp-Galactose-4-Epimerase; Sir2 Fam; Transcriptional Repressor Ethr; Transducin-Al Udpglenac Pyrophosphorylase; Udp-Glucose 4-Epimerase; pha; Transferrin Receptor Protein; Transforming Growth Udp-Glucose 4-Epimerase; UDP-glucose 6-dehydrogenase; Factor-Beta 3: Transforming Protein P21/H-Ras-1; Trans Udp-Glucose Dehydrogenase; UDP-glucuronosyltrans forming Protein Rhoa: Transhydrogenase Diii; Transient ferase 1-9 precursor, microsomal; Udp-N-Acetylenolpyru Receptor Potential-Related Protein; Transitional Endoplas Voylglucosamine Reductas, Udp-N-Acetylglucosamine mic Reticulum Atpas. Transitional Endoplasmic Reticulum 1-Carboxyvinylt: Udp-N-Acetylglucosamine 1-Carboxyvi Atpase; Transketolase; Transketolase-like 1; Translation nyl-Trans; UDP-N-acetylglucosamine 1-carboxyvinyltrans Elongation Factor Selb: Translation Initiation Factor Eif4E: ferase: Udp-N-Acetylglucosamine 2-Epimerase: Udp-N- Translation Initiation Factor If2/EifSB; Transpeptidase (bac Acetylglucosamine Enolpyruvyl Tran; Udp-N- terial); Transposase Inhibitor Protein From Tn5: Trans-Siali Acetylglucosamine Enolpyruvyl Transfer, Udp-N- dase; Transthyretin: Transthyretin precursor; Transthyretin Acetylglucosamine Pyrophosphorylase; Udp-N- Thr119Met Variant; Trehalose Operon Repressor; Triacylg Acetylglucosamine-1-Phosphate Uridyltr; Udp-N- lycerol Lipase, Gastric: Triacyl-Glycerol-Hydrolase; Tri Acetylglucosamine-N-Acetylmuramyl-, Udp-N- chodiene Synthase; Trichotoxin A50E: Tricorn Protease: Acetylmuramate-Alanine Ligase; Udp-N-Acetylmuramate Trifunctional enzyme alpha Subunit, mitochondrial precur L-Alanine Ligase; Udp-N-Acetylmuramoylalanyl-D- sor; Trigger Factor; Triggering Receptor Expressed On Glutamate-:Udp-N-Acetylmuramoyl-L-Alanine: D-Glutam: Myeloid Cel; Trihydroxynaphthalene Reductase; Trimethy Udp-N-Acetylmuramoyl-L-Alanine: D-Glutamate; Udp-N- lamine Dehydrogenase; Triose Phosphate Isomerase; Triose Acteylglucosamine Pyrophosphorylas, Ulex EuropaeuS Lec phosphate Isomerase; Triosephosphate Isomerase, Glycoso tin II: Ultraspiracle Protein: UMP-CMP kinase; Uncoordi mal:Trk System Potassium Uptake Protein Trika Hom:tRNA: nated protein 63: Unknown Protein: Unknown Protein From tRNA Cca-Adding Enzyme; tRNA Nucleotidyltransferase: 2D-Page; Unlocked Metal-Free Concanavalin A; Unsatur tRNA-Guanine Transglycosylase; Tropinone Reductase-I; ated Glucuronyl Hydrolase; Upf)230 Protein Tm 1468; Tropinone Reductase-II; Troponin C, Slow Skeletal and Car Upper Collar Protein; Uracil Phosphoribosyltransferase: diac Muscles; Troponin I, cardiac muscle; Troponin T. car Uracil-DNA Glycosylase; Uracil-DNA Glycosylase Inhibi diac muscle; Trp Operon Repressor; Trp Repressor Binding tor; Ure2 Protein: Urease alpha subunit; Uricase; Uridine Protein Wrba; Trp RNA-Binding Attenuation Protein Com Diphospho-N-Acetylenolpyruvylglucosa; Uridine Phospho plexed: Trypanothione Oxidoreductase; Trypanothione rylase; Uridine Phosphorylase, Putative; Uridine-Cytidine Reductase; Tryparedoxin II; Trypsin; Trypsin I; Trypsin II, Kinase 2; Uridylate Kinase; Uridylmonophosphate/Cytidyl Anionic: Trypsin Inhibitor Bgit; Trypsin Inhibitor I; Trypsin monophosphate Kin; Urocanase Protein, Urocanate Iva; Trypsinogen; Tryptamine D receptors (5HT2B); Tryp Hydratase; Urokinase; Urokinase-Type Plasminogen Activa tophan 2,3-dioxygenase; Tryptophan 5-hydroxylase 1: Tryp tor; Uroporphyrin-III C-Methyltransferase; Uroporphyrino tophan 5-hydroxylase 2; Tryptophan 5-Monooxygenase; gen Decarboxylase; Vacuolar ATP Synthase Subunit C; Valyl Tryptophan Synthase Alpha Chain; Tryptophan Synthase tRNA synthetase: Vanadium Bromoperoxidase; Vanillyl Alpha Chain, Chloroplast; Tryptophan-tRNA Ligase; Tryp Alcohol Oxidase; Variant Surface Glycoprotein; Vascular tophanyl-tRNA Synthetase: Tt0826; Ttk00300 1606: Tubby endothelial growth factor; Vascular endothelial growth factor Protein; Tubulin; Tubulin alpha chain; Tubulin alpha-1 chain; receptor 2 precursor; Vascular endothelial growth factor Tubulin alpha-2 chain; Tubulin alpha-3 chain; Tubulin receptor 3 precursor; Vascular Endothelial Growth Factor alpha-6 chain; Tubulin alpha-8 chain; Tubulin alpha-ubiqui Toxin; Vasopressin V1 a receptor; Vasopressin V1b receptor; tous chain; Tubulin beta chain; Tubulin beta-1 chain; Tubulin Vasopressin V2 receptor; Vasopressin V2 receptor, Neuro beta-2C chain; Tubulin beta-3 chain; Tubulin beta-4 chain; physin 2; Venom Serine Proteinase; Venom Serine Protein Tubulin beta-4q chain; Tubulin-Specific Chaperone A: ase: Vesicular Monoamine Transporter; Vhh-R2 Anti-Rró Tumor Necrosis Factor Alpha; Tumor necrosis factor precur Antibody; Vim-2 Metallo-Beta-Lactamase: Vimentin; Viral sor; Type 2 Malate/Lactate Dehydrogenase; Type 2 Rhinovi guanylyltransfearse; Viral RNA polymerase: Virb11 rus 3C Protease; Type 4 Pilin: Type II DNA Topoisomerase Vi Homolog; Vitamin B12 Receptor; Vitamin B12 Transport Subunit B: Type II Quinohemoprotein Alcohol Dehydrogena; Protein Btuf Vitamin D Binding Protein; Vitamin D Recep Type III Chloramphenicol Acetyltransferase; Type III phos tor; Vitamin D3 Receptor; Vitamin D-Dependent Calcium phodiesterase; Type III Secretion Chaperone Syce; Type T Binding Prote: Vitamin K Reductase; Vitamin K-dependent Voltage gated calcium channel; Type-1 angiotensin 11 Recep protein Z: Voltage gated Sodium channel; Voltage-dependent tor (AT1); Tyrosinase precursor: Tyrosine 3-Monooxyge L-type calcium channel alpha-1C Subunit; Voltage-dependent nase; Tyrosine Aminotransferase; Tyrosine Phenol-Lyase; L-type calcium channel beta-1 subunit; Voltage-dependent Tyrosine Phosphatase; Tyrosine-protein kinase ABL2: P/O-type calcium channel alpha-1A Subunit; Voltage-depen Tyrosine-Protein Kinase Btk; Tyrosine-Protein Kinase Itk/ dent T-type calcium channel: Voltage-Gated Potassium Chan Tsk; Tyrosine-Protein Kinase Receptor Tyro3: Tyrosine-Pro nel: Voltage-gated sodium channel; Volvatoxin A2; Vp 1 Pro tein Kinase Syk; Tyrosine-Protein Kinase Zap-70; Tyrosine tein; Vp39; Vsv Matrix Protein; V-Type Sodium ATP protein phosphatase, non-receptor type 1; Tyrosyl-tRNA Synthase Subunit K: W224H Variant Of S. Enterica Rimla US 2008/0220441 A1 Sep. 11, 2008 92

Bound To U; Wbpp. Wheat Germ. Agglutinin; Winged Bean 28. The source of claim 25, further comprising a collimator Lectin; Wiskott-Aldrich Syndrome Protein; Wunen-Non disposed between the source and the protein sample. functional Gfp Fusion Protein; Xaa-Pro Aminopeptidase; 29. An X-ray microscope for measuring a sample compris Xaa-Pro Dipeptidase; Xanthan Lyase: Xanthine Dehydroge 1ng: nase; Xanthine oxidase; Xanthine Phosphoribosyltrans an X-ray source disposed so as to be able to expose the ferase: Xanthine-Guanine Phosphoribosyltransferase: Xan sample to X-rays; thosine Phosphorylase; Xenobiotic Acetyltransferase: a detector disposed so as to be able to detect the X-ray Xylanase; Xylanase 10C; Xylanase Inhibitor Protein I; Xyla fluorescence of the sample: nase Y; Xyloglucan Endotransglycosylase; Xylose a recording means for making a record of the X-ray fluo Isomerase: Xylose Reductase: Xylose Reductase; Y177F rescence; and Variant Of S. Enterica Rimla Bound To U; Yajq Protein; a record-control means. YdrS33C Protein: Yeast Cytochrome C Peroxidase; Yeast 30. The X-ray microscope of claim 29 where the record Iso-1-Ferrocytochrome C;Yeco:Yfua:Yibi Protein:YigfPro control means ensures the authenticity of the record. tein: Ykof:Ylmd Protein Sequence Homologue:Ylr011Wp: 31. The X-ray microscope of claim 29 where the record Ynk-Contryphan: Yvrk Protein: Zervamicin lib; Zinc Finger control means ensures the integrity of the record. Y-Chromosomal Protein; and Zinc-Alpha-2-Glycoprotein. 32. The X-ray microscope of claim 29 where the record 19. The method of claim 1, wherein the unbound chemical control means ensures the confidentiality of the record. is separated via gel filtration or another size exclusion tech 33. The X-ray microscope of claim 29 where the record nique, and an aliquot from each sample is spotted onto a control means further comprises document encryption. substrate for XRF measurement. 34. The X-ray microscope of claim 29 where the record 20. A system for determining the binding constants of a control means further comprises at least one digital signature. chemical and a receptor, comprising a process for equilibrat 35. The digital signature of claim 34 further comprising the ing the chemical with the protein by incubating the chemical printed name of the signer. and protein in solution for sufficient time to ensure that 36. The digital signature of claim 34 further comprising the chemical equilibrium is obtained; separating the unbound date and time when the signature was executed. chemical in less than 5 minutes at 37 degrees Celsius, and 37. The digital signature of claim 34 further comprising the determining the X-ray fluorescence signal of the chemical, meaning associated with the signature. and converting the X-ray fluorescence signal to a concentra 38. The digital signature of claim 34 where the meaning is tion. selected from the group comprising review, approval, respon 21. A system for determining the binding constants of a sibility, and authorship. chemical and a receptor, comprising a process for equilibrat 39. The digital signature of claim 34 further comprising a ing the chemical with the protein by incubating the chemical linking means whereby the record and the signature are and protein in solution for sufficient time to ensure that linked. chemical equilibrium is obtained; separating the unbound 40. The digital signature of claim 34 where the digital chemical in less than 5 minutes at 37 degrees Celsius, and signature is unique to one individual. determining the X-ray fluorescence signal of the chemical. 41. The digital signature of claim 40 where the signature is 22. A method for analyzing samples comprising depositing based on at least one biometric measurement. an aqueous sample on a focusing chip, allowing the sample to 42. The digital signature of claim 40 where the signature dry, and analyzing the sample using X-ray fluorescence. employs at least two identification components. 23. An apparatus for measuring protein characteristics 43. The digital signature of claim 42 where at least one comprising an X-ray fluorescence spectrometer, a protein, and component is selected from the group comprising: an identi a security system comprising at least one of the security fication code and a password. controls selected from the list of a biometric analysis system, 44. The digital signature of claim 40 comprising a first a closed system, digital signatures, digital signatures config signature and a second signature, the first signature compris ured so that no two individuals have the same combination of ing a plurality of components and the second signature com identification code and password. prising at least one component that is only executable by and 24. A method for analyzing protein purity, comprising designed only to be used by the individual, where the second exposing a protein sample to X-rays, measuring any X-ray signature is provided after the first signature and where the fluorescence, converting the X-ray fluorescence signals of the first signature and the second signature are both provided elements measured into molar ratios, and comparing the during a single, continuous period of controlled system molar ratios of the elements measured to a control value. aCCCSS, 25. An apparatus comprising an X-ray source, and X-ray 45. The digital signature of claim 34 further comprising detector, a protein sample deposited on a Substrate, the Sub means of ensuring that attempted use of the individual's digi strate having a thickness of between 20 nanometers and 25 tal signature by anyone other than the individual requires the microns, and a focusing optic disposed between the protein collaboration of a plurality of individuals. and the X-ray Source. 46. The record-control means of claim 15 further compris 26. The apparatus of claim 25, wherein the X-ray source ing a means of maintaining the uniqueness of the digital emits a beam of X-rays, and wherein the beam of X-rays signature. irradiates an area of between one square nanometer and 3 47. A method for monitoring a protein composition, the Square microns. method comprising the steps of 27. The apparatus of claim 25, wherein the X-ray source exposing the protein composition to X-rays; emits a beam of X-rays and wherein the beam of X-rays irra measuring the amount of Sulfur in the protein composition diates across-sectional area that is between 25% and 250% of by measuring the X-ray fluorescence in the Sulfur spec the area of the protein sample. trum; US 2008/0220441 A1 Sep. 11, 2008

measuring the amount of a non-sulfur element in the pro measuring the amount of Sulfur in the protein composition tein composition by measuring the X-ray fluorescence in by measuring the X-ray fluorescence in the Sulfur spec the non-Sulfur-element spectrum; and trum; calculating the relative ratio of the amount of the sulfur and the amount of the non-sulfur element, thus monitoring measuring the amount of protein in the protein composi the protein composition. tion by measuring the absorbance of the light having a 48. A method for monitoring the purity of a protein com wavelength of about 260 nmi; and position, the method comprising the steps of: calculating the relative ratio of the amount of sulfur a the exposing the protein composition to X-rays; amount of protein. exposing the protein composition to light having a wave length of about 260 nm,