US 20100316643A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0316643 A1 Eckert et al. (43) Pub. Date: Dec. 16, 2010

(54) TARGETED ANTIMICROBIAL MOIETIES Related U.S. Application Data (60) Provisional application No. 61/224,825, filed on Jul. (75) Inventors: Randal H. Eckert, Redondo Beach, 10, 2009, provisional application No. 61/150,287, CA (US); Daniel Yarbrough, Los filed on Feb. 5, 2009. Angeles, CA (US); Wenyuan Shi, O O Los Angeles, CA (US); Maxwell Publication Classification Anderson, Sequim, WA (US); Jian (51) Int. Cl. He, Los Angeles, CA (US); Chris A 6LX 39/395 (2006.01) Kaplan, Los Angeles, CA (US); C07K 7/08 (2006.01) Jee-Hyun Sim, Garden Grove, CA C07K I4/00 (2006.01) (US) C07K 9/00 (2006.01) A638/16 (2006.01) Correspondence Address: Y. ity 30.8 TOWNSEND AND TOWNSEND AND CREW, A6IP3L/04 (2006.015 LLP TWO EMBARCADERO CENTER, EIGHTH A6IP3 L/10 (2006.01) FLOOR A6IP33/02 (2006.01) SAN FRANCISCO, CA 94111-3834 US A6IP3L/2 (2006.01) 9 (US) (52) U.S. Cl...... 424/134.1; 530/326; 530/324; (73) Assignee: The Regents of the University of 530/387.3; 514/21.3; 514/21.4; 435/34;977/774 California, Oakland, CA (US) (57) ABSTRACT This invention provides novel targeted antimicrobial compo (21) Appl. No.: 12/701,443 sitions. In various embodiments chimeric moieties are pro vided comprising an antimicrobial peptide attached to a pep (22) Filed: Feb. 5, 2010 tide targeting moiety that binds a bacterial Strain or species. Patent Application Publication Dec. 16, 2010 Sheet 1 of 19 US 2010/0316643 A1

Formula I

(91) R= -CH-CH (92) R = W (93) R = Et P = CHCHCOR, (94) R = -H R = H, alkyl, alkoxyl, alkenyl or alkynyl, (95) R = -COCH all from C to C, but preferably H (96), R = -CHO Me = methyl (97) pH R = -CH-CHOH (98) R = -CH=CHCOH (99), R = PR

FIG. 1

Patent Application Publication Dec. 16, 2010 Sheet 3 of 19 US 2010/0316643 A1

N NN N X

compound M x Y 19 2 SC), 121 HOSiOSCH, CH, N(CH). H 123

125 Z CH, N, 2 126 Z: SON (CHOHOFi) 126 A. SOH

FIG. 3 Patent Application Publication Dec. 16, 2010 Sheet 4 of 19 US 2010/0316643 A1

2. N. . s 2. N. ? | - N. - N N N Cu H - ---

N

MonastIal Fast Blue E Monast Ial Fast Blue phthalocyanine) (CI PigittentBlue 15)

FIG. 4 Patent Application Publication Dec. 16, 2010 Sheet 5 of 19 US 2010/0316643 A1

X R’ 2-1

S+ R Y R

R R R X Y

Methylene blue (CH3)2N N(CH3)2 H N S Toluidine blue O (CH)N NH CH N S Neutral red (CH)N NH CH N NH Proflavine HN NH H CH NH Acridine orange (CH),N N(CH) H CH NH Aminacrine H H H C-NH NH Ethacridine HN H OCH5 C-NH. NH

Merocyanine-type

NaOS Dicarbocyanine-type X R X S21a2N2nal I

X R X R Merocyanines Dicarbocyanines - O (MC540) S Et S Se H Se O (DHOCI)

FIG. 6 Patent Application Publication Dec. 16, 2010 Sheet 6 of 19 US 2010/0316643 A1

4' 5 4. / N N 3 5 2 W X Y 2 1.

Psoraiens Angelicins

W X Y Z

O CH O O psoralen S CH O O thienocountarin O N O O 8-azacoumarin O CH O S 2-thiofuranOCoumarin O CH () Se 2-Selenofuranocoumarin

FIG. 7

HO O OH

HO 21 Me

HO Me

HO O OH O H Hypericin Perylenequinonoids R R R R

R/R -CHC(OH)MeCH(COMe)- OMe OMe hypocrellin A RJR -CI ICMe=C(COMe)- OMe OMe hypocrellin B -CHCHMeCOPh -CHCHMeOCO-p-CHOH OMe OMe. Calphostin C

FIG. 8 Patent Application Publication Dec. 16, 2010 Sheet 7 of 19 US 2010/0316643 A1

FIG. 9 Patent Application Publication Dec. 16, 2010 Sheet 8 of 19 US 2010/0316643 A1

Ns s s sS

s - f s

Y. 8 &. R sSS ^ Y & SS. SS's S. SS S S.s S S S 'SS s s & s & & s R Y. s s s Patent Application Publication Dec. 16, 2010 Sheet 9 of 19 US 2010/0316643 A1

E1

Sarassssssssssssssssssssssssssssssssssars

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S*:::::::::::::::::

swy S.s

S. S. S.

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xxx xxxx xxxxx xxxx xxxxx xxxx xxxxx xxxx xxxxx xxxx xxxxx xxxxx xxxx

SYYYYYYYYYYss SSSSSWSSSSSSSSWSSSSSSSSS E.

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s S K X X S S

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Syrissyrsssssssssssssssssssssy sees

S-axxx-xx-xx-xx-aa-S S Sa.S

xxxxxxxxxxxYxxxxx

FIG. 12 Patent Application Publication Dec. 16, 2010 Sheet 10 of 19 US 2010/0316643 A1

TFFRFLNRG GG-k^\f RKFLKKWLL KKHRKHRKHRKHGGG MH(KH)-20 (mw 4884.91) DAANEAGGG-k^M FIRKFLKKWLL KKHRKHRKHRKHGGG BL(KH)-20 (mw 4373.4) TFFRFLNRGGG-k^M FIRKFLKKWLL DAAN EAGGG M8(BL)-20 (mw 3798.01)

FIG. 13 Patent Application Publication Dec. 16, 2010 Sheet 11 of 19 US 2010/0316643 A1

8)

CO

mAU -0

()

()

S.() (). S() ().() Retention volume (mL)

FIG. 14A Patent Application Publication Dec. 16, 2010 Sheet 12 of 19 US 2010/0316643 A1

is&'s sk sess is

Mass (m/z)

FIG. 14B Patent Application Publication Dec. 16, 2010 Sheet 13 of 19 US 2010/0316643 A1

- BLOKH)-20 - -I-M8(KH-20 iron

M8(BL)-20

| -- BD2.20 s “No Peptide

FIG. 15A

. -e-BLKH)-20

. --M80KH)-20

were B.

2 3. s 5 f Time (h)

FIG. 15B Patent Application Publication Dec. 16, 2010 Sheet 14 of 19 US 2010/0316643 A1

r(- BL(KH)-20 --M8(KH-20 -A-M8(BL-20 ^ - B).() & -- Ne Peptide 1 -

s 5 6 Time (i) FIG. 15C

-e- BL(KH-20 f --M8(KH-20 -& s -

1.4 rth- AE8(BL)-20 - -e- BD2.20 a.

2 s S 6 Time (h

FIG. 15D Patent Application Publication Dec. 16, 2010 Sheet 15 of 19 US 2010/0316643 A1

... " -e-BL(KH)-20 ... " -- M8(KH-20 -A-M8(BL-20 . who B). 1 -i- No Peptide .9

2. S { Tinae (h)

FIG. 15E

1E04 ; 1E03 1E02

iu. researrarae us stasksvaawaak rural SI8(K-20 vis(BL-20 BLKEI-20 3). titrates

FIG. 16 Patent Application Publication Dec. 16, 2010 Sheet 16 of 19 US 2010/0316643 A1

ZL‘61-I

Patent Application Publication Dec. 16, 2010 Sheet 18 of 19 US 2010/0316643 A1

s

:

S. s rs w

se s s C. cs S S S to r *t ri test83 series assaarea Patent Application Publication Dec. 16, 2010 Sheet 19 of 19 US 2010/0316643 A1

O4

O.35 -

O.3 -

0.25 -

FIG. 20 US 2010/0316643 A1 Dec. 16, 2010

TARGETED ANTIMICROBAL MOIETIES more effector disclosed herein. Any targeting moiety dis closed herein can be attached to any one or more antimicro CROSS-REFERENCE TO RELATED bial peptide disclosed herein. APPLICATIONS 0008. In certain embodiments chimeric moieties are pro vided where the chimeric moieties comprise an effector 0001. This application claims priority to U.S. Provisional attached to a peptide targeting moiety comprising or consist Application No. 61/150,287, filed Feb. 5, 2009; and to U.S. ing of the amino acid sequence of a peptide found in Table 2 Provisional Application No. 61/224,825, filed Jul. 10, 2009, and/or Table 15. In certain embodiments the targeting peptide the disclosures of which are incorporated herein by reference comprises or consists of amino acid or retro or inverso or in their entirety for all purposes. retro-inverso sequence or beta sequence of a peptide found in Table 2 and/or Table 15. In certain embodiments the effector STATEMENT OF GOVERNMENTAL SUPPORT comprises a moiety selected from the group consisting of a detectable label, an antimicrobial peptide, an antibiotic, and a 0002. Not Applicable photosensitizer. In certain embodiments the effector com prises an antimicrobial peptide comprising the amino acid FIELD OF THE INVENTION sequence of a peptide found in Table 2, and/or Table 8, and/or Table 9, and/or Table 10. In certain embodiments the effector 0003. The present invention relates to novel targeting pep comprises an antibiotic found in Table 7. In certain embodi tides, novel antimicrobial peptides, chimeric moieties com ments the effector comprises a photosensitizer. In certain prising novel targeting and/or novel antimicrobial peptides embodiments the photosensitizer is selected from the group and uses thereof. consisting of a porphyrinic macrocycle, a porphyrin, a chlo rine, a crown ether, an acridine, an azine, a phthalocyanine, a BACKGROUND OF THE INVENTION cyanine, a psoralen, and a perylenequinonoid. In certain 0004 Antibiotic research at the industrial level was origi embodiments the photosensitizing agent is an agent shown in nally focused on the identification of refined variants of any of FIGS. 1-11. already existing drugs. This resulted example, in the devel 0009. Also provided is a chimeric construct comprising a opment of antibiotics such as newer penicillins, cephalospor targeting moiety attached to an antimicrobial peptide where ins, macrollides, and fluoroquinolones. the antimicrobial peptide comprises or consists of the amino 0005. However, resistance to old and newer antibiotics acid or retro or inverso or retro-inverso sequence of a peptide among bacterial pathogens is evolving rapidly, as exemplified found in Table 2. In certain embodiments the targeting moiety by extended beta-lactamase (ESBL) and quinolone resistant is a peptide that comprises or consists of the amino acid or gram-negatives, multi-resistant gonococci, methicillin resis retro or inverso or retro-inverso or beta sequence of a peptide tant Staphylococcus aureus (MRSA), Vancomycin resistant found in Table 2, and/or Table 3, and/or Table 4, and/or Table enterococci (VRE), penicillin non-susceptible pneumococci 6, and/or Table 15. In certain embodiments, the targeting (PNSP) and macrollide resistant pneumococci and strepto moiety comprises an antibody (e.g., an antibody identified in cocci (see, e.g., Panlilo et al. (1992) Infect. Control Hosp. Table 5). In certain embodiments the targeting moiety is Epidemiol., 13: 582-586: Morris et al. (1995) Ann Intern chemically conjugated to the effector directly or via a linker. Med., 123: 250-259, and the like). An overuse, or improper In certain embodiments the targeting moiety is chemically use, of antibiotics is believed to be of great importance for conjugated to the effector via a linker comprising a polyeth triggering and spread of drug resistant bacteria. Microbes ylene glycol (PEG). In certain embodiments the targeting have, in many cases, adapted and are resistant to antibiotics moiety is chemically conjugated to the effector via a non due to constant exposure and improper use of the drugs. peptide linker found in Table 11. In certain embodiments the 0006 Drug resistant pathogens represent a major eco where the targeting moiety is linked to the effector via a nomic burden for health-care systems. For example, postop peptide linkage. In certain embodiments the chimeric con struct is a fusion protein. In certain embodiments the linker is erative and other nosocomial infections will prolong the need a peptide linker found in Table 11. In certain embodiments the for hospital care and increase antibiotic drug expenses. It is chimeric moiety is functionalized with a polymer (e.g., poly estimated that the annual cost of treating drug resistant infec ethylene glycol, a cellulose, a modified cellulose, etc.) to tions in the United States is approximately $5 billion. increase serum halflife. SUMMARY OF THE INVENTION 0010 Also provided are pharmaceutical compositions comprising the chimeric construct(s)/chimeric moieties 0007. In certain embodiments, novel targeting moieties described herein in a pharmaceutically acceptable carrier. In (e.g., peptides) that specifically/preferentially bind to micro certain embodiments the composition is formulated as a unit organisms (e.g., certain bacteria, yeasts, fungi, molds, dosage formulation. In certain embodiments the composition viruses, algae, protozoa, and the like) are provided. The tar is formulated for administration by a modality selected from geting moieties can be attached to effectors (e.g., detectable the group consisting of intraperitoneal administration, topical labels, drugs, antimicrobial peptides, etc.) to form chimeric administration, oral administration, inhalation administra constructs for specifically/preferentially delivering the effec tion, transdermal administration, Subdermal depot adminis torto and/or into the target organism. In certain embodiments tration, and rectal administration. novel antimicrobial peptides that can be used to inhibit (e.g., 0011. Also provided is an antimicrobial composition com kill and/or inhibit growth and/or proliferation) of certain prising an isolated antimicrobial moiety comprising or con microorganisms (e.g., certain bacteria, yeasts, fungi, molds, sisting of the amino acid sequence of a peptide found in Table viruses, algae, protozoa, and the like) are provided. Any tar 2. In certain embodiments the peptide comprises or consists geting moiety disclosed herein can be attached to any one or of the amino acid or retro or inverso or retro-inverso sequence US 2010/0316643 A1 Dec. 16, 2010

or beta sequence of a peptide found in Table 2. In certain 0014. In various embodiments methods are provided for embodiments the peptide is a peptide selected from the group detecting a microorganism (e.g., bacteria, yeast, protozoan, consisting of a peptide consisting of the amino acid sequence virus, algae, fungi, etc.) or biofilm comprising the microor of a peptide found in Table 2 comprising all L residues, a ganism. The methods typically involve contacting the micro peptide consisting of the amino acid sequence of a peptide organism or biofilm with a composition comprising a detect found in Table 2 comprising a peptide found in Table com able label attached to a targeting peptide comprising the prising all D residues, a peptide comprising the inverse of an amino acid sequence of a peptide comprising or consisting of amino acid sequence found in Table 2, a peptide comprising the amino acid or retro or inverso or retro-inverso sequence of the retro-inverso form of a peptide found in Table 2, a peptide a peptide found in Table 2; and detecting the detectable label where the quantity and/or location of the detectable label is an found in Table 2 comprising a conservative Substitution, and indicator of the presence of the microorganism and/or biofilm a peptide found in Table 2 comprising a substitution of a film. In certain embodiments the microorganism or biofilm is naturally occurring amino acid with a non-naturally occur a bacterium or a bacterial film. In certain embodiments the ring amino acid. In certain embodiments the peptide com detectable label is a label selected from the group consisting prises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conservative of a radioactive label, a radio-opaque label, a fluorescent dye, Substitutions. a fluorescent protein, an enzymatic label, a colorimetric label, 0012. Also provided is a composition comprising an iso and a quantum dot. lated targeting moiety comprising or consisting of the amino 0015. In certain embodiments compositions are also pro acid sequence of a peptide found in Table 2 or Table 15. In vided comprising a photosensitizing agent attached to a tar certain embodiments the peptide comprises or consists of the geting peptide where the targeting peptide comprising or amino acid or retro or inverso or retro-inverso sequence or consisting of the amino acid or retro or inverso or retro beta sequence of a peptide found in Table 2 or Table 15. In inverso sequence of a peptide found in Table 2 or Table 15. In certain embodiments the peptide is a peptide selected from certain embodiments the photosensitizing agent is an agent the group consisting of a peptide consisting of the amino acid selected from the group consisting of a porphyrinic macro sequence of a peptide found in Table 2 or Table 15 comprising cycle, a porphyrin, a chlorine, a crown ether, an acridine, an all L residues, a peptide consisting of the amino acid sequence azine, a phthalocyanine, a cyanine, a psoralen, and a peryle of a peptide found in Table 2 comprising a peptide found in nequinonoid. In certain embodiments the photosensitizing Table comprising all D residues, a peptide comprising the agent is an agent shown in any of FIGS. 1-11. In certain inverse of an amino acid sequence found in Table 2 or Table embodiments the photosensitizing agent is attached to the 15, a peptide comprising the retro-inverso form of a peptide targeting peptide by a non-peptide linker. In certain embodi found in Table 2 or Table 15, a peptide found in Table 2 or ments photosensitizing agent is attached to the targeting pep Table 15 comprising a conservative Substitution, and a pep tide by a linker comprising a polyethylene glycol (PEG). In tide found in Table 2 or Table 15 comprising a substitution of certain embodiments the photosensitizing agent is attached to a naturally occurring amino acid with a non-naturally occur the targeting peptide by a non-peptide linker found in Table ring amino acid. In certain embodiments the peptide com 11. prises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conservative 0016. In certain embodiments methods are provided for Substitutions. inhibiting the growth or proliferation of a microorganism 0013. In certain embodiments methods are provided for and/or a biofilm (e.g., a bacterium and/or a bacterial film), inhibiting the growth and/or proliferation of a microorganism where the methods involve contacting the a microorganism and/or a biofilm comprising a microorganism. The methods and/or a biofilm with a composition comprising a photosen typically involve contacting the microorganism or biofilm sitizing agent attached to a targeting peptide as described with a composition comprising an antimicrobial peptide com herein. In certain embodiments the method further comprises prising or consisting of the amino acid sequence of a peptide exposing the microorganism or biofilm to a light source. In found in Table 2 (e.g., the amino acid or retro or inverso or certain embodiments the microorganism is a microorganism retro-inverso sequence or beta sequence of a peptide found in selected from the group consisting of a bacterium, a yeast, a Table 2); and/or contacting the microorganism or biofilm with fungus, a protozoan, and a virus. In certain embodiments the a composition comprising an antimicrobial moiety attached biofilm comprises a bacterial film. to a targeting peptide comprising or consisting of the amino 0017. In certain embodiments chimeric moieties are pro acid sequence of a peptide found in Table 2 (e.g., the amino vided wherein the chimeric moiety comprises multiple tar acid or retro or inverso or retro-inverso sequence or beta geting moieties attached to each other. In certain embodi sequence of a peptide found in Table 2). In certain embodi ments the targeting moieties are directly attached to each ments the microorganism or biofilm is a bacterium or a bac other. In certain embodiments the targeting moieties are terial film. In certain embodiments the targeting peptide is attached to each other via a peptide linker. In certain embodi chemically conjugated to the antimicrobial peptide. In certain ments the targeting moieties are attached to each other via a embodiments the targeting peptide is linked directly to the non-peptide linker. In certain embodiments chimeric moi antimicrobial peptide. In certain embodiments the targeting eties are provided wherein the chimeric moiety comprises peptide is linked to the antimicrobial peptide via a linker multiple effectors attached to each other. In certain embodi comprising a polyethylene glycol. In certain embodiments ments the effectors are directly attached to each other. In the targeting peptide is linked to the antimicrobial peptide via certain embodiments the effectors are attached to each other a non-peptide linkage in Table 11. In certain embodiments the via a peptide linker. In certain embodiments the effectors are targeting peptide is linked to the antimicrobial peptide via a attached to each other via a non-peptide linker. peptide linkage. In certain embodiments the targeting peptide 0018. In certain embodiments chimeric moieties are pro linked to the antimicrobial peptide is a fusion protein. In vided where the chimeric moiety comprises one or more certain embodiments the linker is a peptide linker in Table 11. targeting moieties attached to one or more effectors. In certain US 2010/0316643 A1 Dec. 16, 2010

embodiments the chimeric moiety comprises one or more of 0023 The terms “conventional and “natural as applied the targeting moieties shown in Table 2, and/or Table 4 and/or to peptides herein refer to peptides, constructed only from the Table 6, and/or Table 15 attached to a single effector. In naturally-occurring amino acids: Ala, Cys, Asp, Glu, Glu, certain embodiments the chimeric moiety comprises one or Phe, Gly, His, Ile, Lys, Leu, Met, ASn, Pro, Gln, Arg, Ser. Thr, more effectors attached to a single targeting moiety. In certain Val, Trp, and Tyr. A compound of the invention “corresponds' embodiments the chimeric moiety comprises one or more to a natural peptide if it elicits a biological activity (e.g., effectors comprising one or more of the antimicrobial pep antimicrobial activity) related to the biological activity and/or tides shown in Table 2, and/or Table 8, and/or Table 9, and/or specificity of the naturally occurring peptide. The elicited Table 10 attached to a single targeting moiety. In certain activity may be the same as, greater than or less than that of embodiments the chimeric moiety comprises multiple target the natural peptide. In general. Such a peptoid will have an ing moieties attached to multiple effectors. essentially corresponding monomer sequence, where a natu ral amino acid is replaced by an N-Substituted glycine deriva DEFINITIONS tive, if the N-substituted glycine derivative resembles the original amino acid in hydrophilicity, hydrophobicity, polar 0019. The term "peptide' as used herein refers to a poly ity, etc. Thus, for example, the following pairs of peptides mer of amino acid residues typically ranging in length from 2 would be considered “corresponding: to about 50 residues. In certain embodiments the peptide ranges in length from about 2, 3, 4, 5, 7, 9, 10, or 11 residues to about 50, 45, 40, 45, 30, 25, 20, or 15 residues. In certain (SEQ ID NO: 1) Ia. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe embodiments the peptide ranges in length from about 8, 9, 10. (Angiotensin II) 11, or 12 residues to about 15, 20 or 25 residues. Where an and amino acid sequence is provided herein, L-, D-, or beta amino acid versions of the sequence are also contemplated as well as (SEQ ID NO: 2) retro, inversion, and retro-inversion isoforms. Peptides also Ib. Asp-Arg-Val* -Tyr-Ile-His-Pro-Phe; include amino acid polymers in which one or more amino (SEQ ID NO : 3) acid residues is an artificial chemical analogue of a corre IIa. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg sponding naturally occurring amino acid, as well as to natu (Bradykinin) rally occurring amino acid polymers. In addition, the term and applies to amino acids joined by a peptide linkage or by other, (SEO ID NO : 4) “modified linkages” (e.g., where the peptide bond is replaced IIb : Arg-Pro-Pro-Gly-Phe-Ser* - Pro-Phe-Arg; by an O.-ester, a B-ester, a thioamide, phosphonamide, carbo (SEO ID NO; 5) mate, hydroxylate, and the like (see, e.g., Spatola, (1983) IIIa : Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr Chem. Biochem. Amino Acids and Proteins 7: 267-357), Pro-Leu-Val-Thr (B-Endorphin) ; where the amide is replaced with a saturated amine (see, e.g., and Skiles et al., U.S. Pat. No. 4,496,542, which is incorporated (SEQ ID NO : 6) herein by reference, and Kaltenbronn et al., (1990) Pp. 969 IIIb : Gly-Gly-Phe-Met-Ser* - Ser-Glu-Lys *-Ser-Gln 970 in Proc. 11th American Peptide Symposium, ESCOM Serk-Pro-Leu-Val-Thr . Science Publishers, The Netherlands, and the like)). 0020. The term “residue” as used herein refers to natural, In these examples, “Val” refers to N-(prop-2-yl)glycine, synthetic, or modified amino acids. Various amino acid ana “Phe' refers to N-benzylglycine, “Ser” refers to N-(2-hy logues include, but are not limited to 2-aminoadipic acid, droxyethyl)glycine, “Leu refers to N-(2-methylprop-1-yl) 3-aminoadipic acid, beta-alanine (beta-aminopropionic glycine, and "Ile refers to N-(1-methylprop-1-yl)glycine. acid), 2-aminobutyric acid, 4-aminobutyric acid, piperidinic The correspondence need not be exact: for example, N-(2- acid, 6-aminocaproic acid, 2-aminoheptanoic acid, 2-ami hydroxyethyl)glycine may substitute for Ser. Thr, Cys, and noisobutyric acid, 3-aminoisobutyric acid, 2-aminopimelic Met; N-(2-methylprop-1-yl)glycine may substitute for Val, acid, 2.4 diaminobutyric acid, desmosine, 2,2'-diami Leu, and Ile. Note in IIIa and IIIb above that Ser is used to nopimelic acid, 2,3-diaminopropionic acid, n-ethylglycine, substitute for Thr and Ser, despite the structural differences: n-ethylasparagine, hydroxylysine, allo-hydroxylysine, 3-hy the sidechain in Ser is one methylene group longer than that droxyproline, 4-hydroxyproline, isodesmosine, allo-isoleu of Ser, and differs from Thr in the site of hydroxy-substitu cine, n-methylglycine, sarcosine, n-methylisoleucine, 6-n- tion. In general, one may use an N-hydroxyalkyl-substituted methyllysine, n-methylvaline, norvaline, norleucine, glycine to Substitute for any polar amino acid, an N-benzyl- or ornithine, and the like. These modified amino acids are illus N-aralkyl-substituted glycine to replace any aromatic amino trative and not intended to be limiting. acid (e.g., Phe, Trp, etc.), an N-alkyl-substituted glycine Such 0021 “B-peptides’ comprise of “Bamino acids, which as N-butylglycine to replace any nonpolar amino acid (e.g., have their amino group bonded to the B carbon rather than the Leu, Val, Ile, etc.), and an N-(aminoalkyl)glycine derivative C-carbon as in the 20 standard biological amino acids. The to replace any basic polar amino acid (e.g., Lys and Arg). only commonly naturally occurring Bamino acid is 3-ala 0024. A “compound antimicrobial peptide' or “com 1C. pound AMP refers to a construct comprising two or more 0022 Peptoids, or N-substituted glycines, are a specific AMPs joined together. The AMPs can be joined directly or subclass of peptidomimetics. They are closely related to their through a linker. They can be chemically conjugated or, natural peptide counterparts, but differ chemically in that where joined directly together or through a peptide linker can their side chains are appended to nitrogen atoms along the comprise a fusion protein. molecule's backbone, rather than to the C-carbons (as they are 0025. In certain embodiments, conservative substitutions in natural amino acids). of the amino acids comprising any of the sequences described US 2010/0316643 A1 Dec. 16, 2010

herein are contemplated. In various embodiments one, two, using a sequence comparison algorithm, test and reference three, four, or five different residues are substituted. The term sequences are input into a computer, Subsequence coordi “conservative substitution' is used to reflect amino acid sub nates are designated, if necessary, and sequence algorithm stitutions that do not substantially alter the activity (e.g., program parameters are designated. The sequence compari antimicrobial activity and/or specificity) of the molecule. son algorithm then calculates the percent sequence identity Typically conservative amino acid Substitutions involve Sub for the test sequence(s) relative to the reference sequence, stitution one amino acid for another amino acid with similar based on the designated program parameters. Optimal align chemical properties (e.g. charge or hydrophobicity). Certain ment of sequences for comparison can be conducted, e.g., by conservative substitutions include “analog substitutions' the local homology algorithm of Smith & Waterman (1981) where a standard amino acid is replaced by a non-standard Adv. Appl. Math. 2: 482, by the homology alignment algo (e.g., rare, synthetic, etc) amino acid differing minimally rithm of Needleman & Wunsch (1970).J. Mol. Biol. 48: 443, from the parental residue. Amino acid analogs are considered by the search for similarity method of Pearson & Lipman to be derived synthetically from the standard amino acids (1988) Proc. Natl. Acad. Sci., USA, 85: 2444, by computer without Sufficient change to the structure of the parent, are ized implementations of these algorithms (GAP, BESTFIT, isomers, or are metabolite precursors. Examples of Such FASTA, and TFASTA in the Wisconsin Genetics Software “analog substitutions” include, but are not limited to, 1) Lys Package, Genetics Computer Group, 575 Science Dr. Madi Orn, 2) Leu-Norleucine, 3) Lys-LysTFA, 4) Phe-Phe(Gly, son, Wis.), or by visual inspection. and 5) 6-amino butylglycine-4-amino hexylglycine, where (0027. The term “specificity” when used with respect to the Phegly refers to phenylglycine (a Phe derivative with a H antimicrobial activity of a peptide indicates that the peptide rather than CH component in the R group), and LysTFA preferentially inhibits growth and/or proliferation and/or kills refers to a Lys where a negatively charged ion (e.g., TFA) is a particular microbial species as compared to other related attached to the amine R group. Other conservative substitu and/or unrelated microbes. In certain embodiments the pref tions include “functional substitutions” where the general erential inhibition or killing is at least 10% greater (e.g., LDso chemistries of the two residues are similar, and can be suffi is 10% lower), preferably at least 20%, 30%, 40%, or 50%, cient to mimic or partially recover the function of the native more preferably at least 2-fold, at least 5-fold, or at least peptide. Strong functional Substitutions include, but are not 10-fold greater for the target species. limited to 1) Gly/Ala, 2) Arg/Lys, 3) Ser/Tyr/Thr, 4) Leu/Ile/ 0028 “Treating or “treatment of a condition as used Val, 5) Asp/Glu, 6) Gln/ASn, and 7) Phe/Trp/Tyr, while other herein may refer to preventing the condition, slowing the functional substitutions include, but are not limited to 8) onset or rate of development of the condition, reducing the Gly/Ala/Pro, 9) Tyr/His, 10) Arg/Lys/His, 11) Ser/Thr/Cys, risk of developing the condition, preventing or delaying the 12) Leu/Ile/Val/Met, and 13) Met/Lys (special case under development of symptoms associated with the condition, hydrophobic conditions). Various “broad conservative sub reducing or ending symptoms associated with the condition, stations include Substitutions where amino acids replace generating a complete or partial regression of the condition, other amino acids from the same biochemical or biophysical or some combination thereof. grouping. This is similarity at a basic level and stems from 0029. The term “consisting essentially of when used with efforts to classify the original 20 natural amino acids. Such respect to an antimicrobial peptide (AMP) or AMP motif as substitutions include 1) nonpolar side chains: Gly/Ala? Val/ described herein, indicates that the peptide or peptides Leu/Ile/Met/Pro/Phe/Trp, and/or 2) uncharged polar side encompassed by the library or variants, analogues, or deriva chains Ser/Thr/ASn/Gln/Tyr/Cys. In certain embodiments tives thereof possess Substantially the same or greater antimi broad-level Substitutions can also occur as paired substitu crobial activity and/or specificity as the referenced peptide. In tions. For example, any hydrophilic neutral pair Ser, Thr, certain embodiments Substantially the same or greater anti Gln, Asn., Tyr, Cys--Ser. Thr, Gln, Asn., Tyr, Cys can may be microbial activity indicates at least 80%, preferably at least replaced by a charge-neutral charged pair Arg, Lys, His+ 90%, and more preferably at least 95% of the anti microbial Asp, Glu. The following six groups each contain amino activity of the referenced peptide(s) against a particular bac acids that are typical conservative Substitutions for one terial species (e.g., S. mutans). another: 1) Alanine (A), Serine (S). Threonine (T); 2) Aspar 0030 The term “porphyrinic macrocycle” refers to a por tic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine phyrin or porphyrin derivative. Such derivatives include por (Q); 4) Arginine (R), Lysine (K), Histidine (H); 5) Isoleucine phyrins with extra rings ortho-fused, or orthoperifused, to the (I), Leucine (L), Methionine (M), Valine (V); and 6) Pheny porphyrin nucleus, porphyrins having a replacement of one or lalanine (F), Tyrosine (Y), Tryptophan (W). more carbon atoms of the porphyrin ring by an atom of 0026. In certain embodiments, targeting peptides, antimi another element (skeletal replacement), derivatives having a crobial peptides, and/or STAMPs compromising at least replacement of a nitrogen atom of the porphyrin ring by an 80%, preferably at least 85% or 90%, and more preferably at atom of another element (skeletal replacement of nitrogen), least 95% or 98% sequence identity with any of the sequences derivatives having Substituents other than hydrogen located at described herein are also contemplated. The terms “identical the peripheral (meso-, ..beta.-) or core atoms of the porphyrin, or percent “identity.” refer to two or more sequences that are derivatives with saturation of one or more bonds of the por the same or have a specified percentage of amino acid resi phyrin (hydroporphyrins, e.g., chlorins, bacteriochlorins, iso dues that are the same, when compared and aligned for maxi bacteriochlorins, decahydroporphyrins, corphins, pyrrocor mum correspondence, as measured using one of the following phins, etc.), derivatives obtained by coordination of one or sequence comparison algorithms or by visual inspection. more metals to one or more porphyrinatoms (metalloporphy With respect to the peptides of this invention sequence iden rins), derivatives having one or more atoms, including pyr tity is determined over the full length of the peptide. For rolic and pyrromethenyl units, inserted in the porphyrin ring sequence comparison, typically one sequence acts as a refer (expanded porphyrins), derivatives having one or more ence sequence, to which test sequences are compared. When groups removed from the porphyrin ring (contracted porphy US 2010/0316643 A1 Dec. 16, 2010

rins, e.g., corrin, corrole) and combinations of the foregoing 0035. The term “STAMP” refers to Specifically Targeted derivatives (e.g. phthalocyanines, porphyrazines, naphthalo Anti-Microbial Peptides. An MH-STAMP is a STAMP bear cyanines, Subphthalocyanines, and porphyrin isomers). Cer ing two or more targeting domains (i.e., a multi-headed tain porphyrinic macrocycles comprise at least one 5-mem STAMP). bered ring. 0036. In various embodiments the amino acid abbrevia 0031. As used herein, an “antibody' refers to a protein tions shown in Table 1 are used herein. consisting of one or more polypeptides Substantially encoded TABL E 1. by immunoglobulin genes or fragments of immunoglobulin genes. The recognized immunoglobulin genes include the Amino acid abbreviations. kappa, lambda, alpha, gamma, delta, epsilon and mu constant Abbreviation region genes, as well as myriad immunoglobulin variable region genes. Light chains are classified as either kappa or Name 3 Letter 1. Luetter lambda. Heavy chains are classified as gamma, mu, alpha, Alanine Ala A. delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, Ig) and IgE, respectively. BAlanine (NH-CH-CH-COOH) Ala 0032. A typical immunoglobulin (antibody) structural Arginine Arg R unit is known to comprise a tetramer. Each tetramer is com posed of two identical pairs of polypeptide chains, each pair Asparagine Asn N having one “light” (about 25 kD) and one “heavy chain Aspartic Acid Asp D (about 50-70 kD). The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids Cysteine Cys C primarily responsible for antigen recognition. The terms vari Glutamic Acid Glu E able light chain (V) and variable heavy chain (V) refer to these light and heavy chains respectively. Glutamine Glin Q 0033 Antibodies exist as intact immunoglobulins or as a Glycine Gly G number of well characterized fragments produced by diges tion with various peptidases. Thus, for example, pepsin Histidine His H digests an antibody below the disulfide linkages in the hinge Homo serine Hse region to produce F(ab)', a dimer of Fab which itself is a light chain joined to V-C1 by a disulfide bond. The F(ab)' may Isoleucine Ile I be reduced under mild conditions to break the disulfide link Leucine Luell L age in the hinge region thereby converting the (Fab') dimer into an Fab' monomer. The Fab' monomer is essentially an Lysine Lys K Fab with part of the hinge region (see, Fundamental Immu Methionine Met M nology, W. E. Paul, ed., Raven Press, N.Y. (1993), for a more detailed description of other antibody fragments). While vari Methionine sulfoxide Met (O) ous antibody fragments are defined in terms of the digestion Methionine methylsulfonium Met (S-Me) - ofan intactantibody, one of skill will appreciate that such Fab' fragments may be synthesized de novo either chemically or Norleucine Nile by utilizing recombinant DNA methodology. Thus, the term antibody, as used herein also includes antibody fragments Phenylalanine Phe either produced by the modification of whole antibodies or Proline Pro P synthesized denovo using recombinant DNA methodologies, including, but are not limited to, Fab', IgG, IgM, IgA, ScPV, Serine Ser S dAb, nanobodies, unibodies, and diabodies. Threonine Thir T 0034. In certain embodiments antibodies and fragments of the present invention can be bispecific. Bispecific antibodies Tryptophan Trp W or fragments can be of several configurations. For example, Tyrosine Tyr Y bispecific antibodies may resemble single antibodies (or anti body fragments) but have two different antigen binding sites Waline Wall W (variable regions). In various embodiments bispecific anti episilon-aminocaproic acid Ahx J bodies can be produced by chemical techniques (Kranz et al. (NH’-(CH2)5-COOH) (1981) Proc. Natl. Acad. Sci., USA, 78: 5807), by “polydoma' techniques (see, e.g., U.S. Pat. No. 4,474,893), or by recom 4-aminobutanoic acid gAbu binant DNA techniques. In certain embodiments bispecific (NH2 (CH) -COOH) antibodies of the present invention can have binding speci tetrahydro isoquinoline-3- O ficities for at least two different epitopes, at least one of which carboxylic acid is an epitope of a microbial organism. The microbial binding antibodies and fragments can also be heteroantibodies. Het Lys (N (epsilon) - trifluoroacetyl) KITFA) eroantibodies are two or more antibodies, orantibody binding C.-aminoisobutyric acid Aib B fragments (e.g., Fab) linked together, each antibody or frag ment having a different specificity. US 2010/0316643 A1 Dec. 16, 2010

BRIEF DESCRIPTION OF THE DRAWINGS 0049 FIG. 13 illustrates various MH-STAMPs used in Example 1. The design, sequence, and observed mass (m/z) 0037 FIG. 1 shows some illustrative porphyrins (com for M8(KH)-20 (SEQ ID NO:7), BL(KH)-20 (SEQ ID pounds 92-99) suitable for use as targeting moieties and/or NO:8), and M8(BL)-20 (SEQID NO:9. antimicrobial effectors. 0050 FIGS. 14A and 14B show HPLC and MS spectra of 0038 FIG. 2 shows some illustrative porphyrins (com M8(KH)-20. The quality of the completed MH-STAMP was pounds 100-118) suitable for use as targeting moieties and/or analyzed by HPLC (FIG. 14A) and MALDI mass spectros antimicrobial effectors. copy (FIG.14B). At UV absorbance 215 nm (260 and 280 nm 0039 FIG. 3 shows some illustrative porphyrins (in par are also plotted), a single major product was detected by ticular phthalocyanines) (compounds 119-128) suitable for HPLC (* retention volume 11.04 mL). After fraction collec use as targeting moieties and/or antimicrobial effectors. tion, the correct mass (m/z) for single-charged M8(KH)-20, 0040 FIG. 4 illustrates the structures of two phthalocya 4884.91 (marked by *), was observed for this peak. Y-axis: nines, Monoastral Fast Blue B and Monoastral Fast Blue G 14A, maU miliabsorbance units; 14B, percent intensity. Suitable for use as targeting moieties and/or antimicrobial 0051 FIG. 15A-15E show growth inhibitory activity of effectors. MH-STAMPs. Monocultures of S. mutans (FIG. 15A); P 0041 FIG.5 illustrates certain azine photosensitizers suit aeruginosa (FIG. 15B); S. epidermidis (FIG.15C); S. aureus able for use as targeting moieties and/or antimicrobial effec (FIG. 15D); or E. coli (FIG.15E); were treated with peptides tors in the compositions and methods described herein. (as indicated in the figure) for 10 min. Agent was then 0042 FIG. 6 shows illustrative cyanine suitable for use as removed and fresh media returned. Culture recovery was targeting moieties and/or antimicrobial effectors in the com measured over time (OD600). Plots represent the average of positions and methods described herein. at least 3 independent experiments with standard deviations. 0043 FIG. 7 shows illustrative psoralen (angelicin) pho 0052 FIG. 16 illustrates the selective activity of dual tosensitizers Suitable for use as targeting moieties and/or targeted and single-targeted MH-STAMPs in mixed culture. antimicrobial effectors in the compositions and methods A mixture of Paeruginosa (Pa), S. mutans (Sm), E. coli (Ec), described herein. and S. epidermidis (Se) planktonic cells were mixed with 0044 FIG. 8 shows illustrative hypericin and the peryle MH-STAMPs (as indicated in the figure) and treated 24 h. nequinonoid pigments suitable for use as targeting moieties After incubation, cfu/mL of remaining constituent species and/or antimicrobial effectors in the compositions and meth were quantitated after plating to selective media. * indicates ods described herein. under 200 surviving cfu/mL recovered. 0045 FIG.9 shows illustrative acridines suitable for use as 0053 FIG. 17 depicts the results of minimal inhibitory targeting moieties and/or antimicrobial effectors in the com concentration (MIC) assays, conducted against S. mutans and positions and methods described herein. a panel of bacteria, including two oral Streptococci, S. San 0046 FIG. 10 illustrates the structure of the acridine Rose guinis and S. sobrinus, to gauge Library 1 STAMP antimi Bengal. crobial activity and S. mutans-selectivity. 0047 FIG. 11 illustrates various crown ethers suitable for 0054 FIG. 18 shows the results of MIC assays utilizing use as targeting moieties and/or antimicrobial effectors in the targeting peptide 2 1 conjugated to one offive AMPs, RWR compositions and methods described herein. WRWF (2c-4), FKKFWKWFRRF (B-33), IKQLLHFFQRF 0048 FIG. 12 schematically shows some illustrative con (B-38), RWRRLLKKLHHLLH (C-11), figurations for chimeric constructs described herein. A: LQLLKQLLKLLKQF (a-7); attached at the C- or N-termi Shows a single targeting moiety T1 attached to a single effec nus, and a linker selected from L1, SGG (L2), L3 and LC. tor E1 by a linker/spacer L. B: Shows multiple targeting MIC assays were conducted against a panel of bacteria, moieties T1, T2, T3 attached directly to each other and including S. mutans (S. mu), S. gordonii (S. gor), S. sanguinis attached by a linker L to a single effector E1. In various (S. san), and S. mitis (S. mit), to gauge differences in activity embodiments T1, T2, and T3, can be domains in a fusion between attaching the targeting peptide to the C- or N-termi protein. C: Shows multiple targeting moieties T1, T2, T3 nus of the AMP region or differences in activity between the attached to each other by linkers L and attached by a linker L linker used. to a single effector E1. In various embodiments T1, T2, and 0055 FIG. 19 shows the killing kinetics of selected pep T3, can be domains in a fusion protein. D: Shows a single tides against oral streptococci. All tested bacteria, (A) S. mitis targeting moiety T1 attached by a linker L to multiple effec (Smit), (B) S. gordonii (Sgor), (C) .S. sanguinis (Ssan), and tors E1, E2, and E3 joined directly to each other. E.: Shows a (D) S. mutans (Smut), were treated with peptide solutions at single targeting moiety T1 attached by a linker L to multiple 25 g/mL for 30s to 2 hand survivors plated. Data represent effectors E1, E2, and E3 joined to each other by linkers L. F: an average of three independent experiments. Shows multiple targeting moieties joined directly to each 0056 FIG. 20 illustrates the inhibitory activity of other and by a linker L to multiple effectors joined to each STAMPs against S. mutans biofilms. Smutans monoculture other by linkers L. G: Shows multiple targeting moieties biofilms were grown and exposed to a 25ug/mL of STAMP. joined to each other by linkers L and by a linker L to multiple unmodified parental AMP or oral antiseptic (for 1 min), effectors joined to each other by linkers L. In various embodi washed, and replenished with fresh medium. Biofilm recov ments T1, T2, and T3, and/or E1, E2, and E3 can be domains ery was monitored after 4 h by A600. Data represent an in a fusion protein. H: Illustrates a branched configuration average of three experiments. where multiple targeting moieties are linked to a single effec tor. I: Illustrates a dual branched configuration where multiple DETAILED DESCRIPTION targeting moieties are linked to multiple effectors. J: Illus trates a branched configuration where multiple targeting moi 0057. In various embodiments this invention is based on eties are linked to multiple effectors where the effectors are the development of a method for the rapid identification and joined to each other in a linear configuration. synthesis of Small peptides from sequenced genomes for the US 2010/0316643 A1 Dec. 16, 2010

purposes of quickly screening these molecules for diverse 0062. In certain embodiments the antimicrobial peptides biological activities. Previously, small secreted peptides had and/or the chimeric moieties described herein can be formu to be identified by direct collection (purification of spent lated with a pharmaceutically acceptable carrier to form a microbial growth medium or biological tissue/fluid), or by pharmacological composition. identification through differential microarray analysis or as a 0063. The amino acid sequences of illustrative peptides of by-product of genetic operon characterization. Both are this invention having antimicrobial and/or targeting activity multi-step processes that terminate at peptide identification; against methicillin resistant Streptococcus mutans, Strepto several separate enterprises are required to synthesize or coccus pyogenes, and/or Treponema denticola is shown in sequence any peptides for characterization. Additionally, Table 2. As with the other peptides described herein, it will be because of their Small size and lack of protein domain recognized that these peptides can comprise all "L' form homologies, Small peptides are frequently overlooked when residues, all “D' form residues, mixtures of “L’ and “D’ describing biological systems, though many organisms con residues, and beta peptide sequences. It will also be appreci ated in addition to the D-form and L-form and beta-peptide tain numerous peptide-sized open reading frames (ORFs). sequences this invention also contemplates retro and retro 0058 Genomic sequence analysis tools already in the pub inverso forms of each of these peptides. In retro forms, the lic domain and high-throughput solid phase peptide chemis direction of the sequence is reversed. In inverse forms, the try were used to rapidly identify and synthesize biologically chirality of the constituent amino acids is reversed (i.e., L active peptides. Using sequences and sometimes annotated form amino acids become D form amino acids and D form genomes, genomes were scanned, by hand or with a search amino acids become L formamino acids). In the retro-inverso algorithm, for ORFs predicted to encode peptides of less than form, both the order and the chirality of the amino acids is for example, 50-60 amino acids (ignoring small tRNA ORFs reversed. Thus, for example, a retro form of the of the peptide or other well characterized genes). Smu11 (MKNLIETVEKFLTYSDEKLEELAKKN 0059. Once noted, these peptides were batch synthesized QALREEISROKSK, SEQ ID NO:11) has the sequence on a multiplex peptide synthesizer, yielding 5-10 mg of each KSKQRSIEERLAQNKKALEELKED peptide that could readily be screened for biological activity SYTLFKEVTEILNKM (SEQID NO:10). Where the Smul1 (e.g., binding activity and/or antimicrobial activity. peptide comprises all L amino acids, the inverse form will 0060 Accordingly, in certain embodiments, this invention comprise all D amino acids and the retro-inverso (retro-in pertains to the identification of novel peptides (see, e.g., Table verse) form will have the sequence of SEQ ID NO:10 and 2) that specifically or preferentially bind particular microor comprise all D form amino acids. Also contemplated are ganisms (e.g., bacteria) and/or that have antimicrobial activ peptides having the amino acid sequences or retroamino acid ity. In certain embodiments these peptides can be attached to sequences of the peptides in Table 2 (or the other tables shown effectors (e.g., drugs, labels, etc.) and used as targeting moi herein) and comprising one, two, three, four, five, six, seven, eties thereby providing a chimeric moiety that preferentially eight, nine, or ten conservative Substitutions, but retaining or specifically delivers the effector to a target microorganism, Substantially the same binding and/or antimicrobial activity. a population of target microorganisms, a microbial film com Also contemplated are peptides having the amino acid prising the target microorganism(s), a biofilm comprising the sequences or retro amino acid sequences of the peptides in target microorganism(s), and the like. Table 2 (or other tables herein) and comprising one, two, 0061. In certain embodiments these peptides can be three, four, five, six, seven, eight, nine, or ten deletions, but exploited for their antimicrobial activity to inhibit the growth retaining Substantially the same binding and/or antimicrobial or proliferation of a microorganism and/or to inhibit the for activity. mation and/or growth of a biofilm comprising the microor 0064. In various embodiments, chimeric moieties com ganism. These antimicrobial peptides can be used alone, in prising one or more of the targeting peptides found in Table 2 conjunction with other agents (e.g., antibacterial agents), and/ attached to one or more effectors (e.g., antimicrobial peptides or they can be coupled to a targeting moiety to provide a as described herein) are contemplated. In various embodi chimeric moiety that preferentially directs the antimicrobial ments, one or more of the antimicrobial peptides found in peptide to a target tissue and/or to a target organism (e.g., a Table 2 used as effectors or attached to one or more targeting bacterium, a population of target microorganisms, a micro moieties (e.g., targeting peptides, targeting antibodies, and bial film, a biofilm, and the like). the like) to form chimeric moieties are contemplated.

TABL E 2 Peptides having antimicrobia and/or targeting activity against one or more of the following: Streptococcus mutans, Streptococcus pyogenes, and Treponema denticola.

SEQ ID Amino Acid Sequence ID NO

Smu11 MKNLIETWEKFLTYSDEKLEELAKKNOALREEISROKSK 11

Smul. 18 GGRAGRIKKLSOKEAEPFEN 12

Smula 1 MFIRSKLRRWDFSGWRRGNKHFLLDKLLITLWK 13

Smul68 MSALFYDTLAAIWISIAGWDARWGH 14

US 2010/0316643 A1 Dec. 16, 2010

TABLE 2 - continued Peptides having antimicrobial and/or targeting activity against one or more of the following: Streptococcus mutans, streptococcus pyogenes, and Treponema denticola.

SEQ ID Amino Acid Sequence ID NO

Smull75 Oc MIFNRRKFFOYFGLSKEAMVEHIOPFILDIWOIHLF 44

Smu1752c GGWLNAISLYGRIG 45

Smull768c GGHKOLVIEPLWSONDOLSLIESLSGILSDSETWDWKDYRSERK 46 EERLKKYESLT

Smul8O8c MTTTOKTYLHIIRELENODIDLIMRSLTSLT 47

Smull 813 MPMTYCGSPRRTDLAVITDEELGOTLEVINHWPRNV 48

Smul882c GGATDGEIIANRMLOGKATKGEITMYTWNIIONGWWNSLWSW 49 GIGGYNSSIGYSAOGNRGFSNYPYDVSMDSDNSSSSSNTTGGY WNYNOSFNSGW

Smu1889c GGLAGAGTGAAWSAPAAEGGGLGPIAGAAIGWDLGAISGAGL SO GWANFCO

Smu1895c GGMTWAEIGAIWGATIGSFYIPNPWIWPFRWR 51

Smu1896c GGFGWDSIWRGFKCWAGTAGTIGTGALGGSATGGLTLPIIGHW 52 SGGIIGGISGAGWGIASFC

Smul899 MLSISORTDRVIVMDKGKIIEEGTHSELIAANGFYHHLFNK 53

Smulle O2c GGAFYORKENVISLDPREWLGFNVTEK 54

Smu1903c GGNIFEYFLE 55

Smu19 Osc GGGRAPRCAALWGASIYDGLAWWGDPWGWAMAAGTIAAGSFC 56

Smu1906c GGCSWKGADKAGFSGGWGGLIGAGGNPWGGWLGIAGGLDAY f GELWGGN

Smulle O7 MEONILNGSYFWLNGKNAKFLLEIDKLTLPDKLATLPWPHOVR 58

Smule 14c GGGRGWNCAAGIALGAGOGYMATAGGTAFLGPYAIGTGAFG 59 AIAGGIGGALNSCG

Smule 15 GGSGSLSTFFRLFNRSFTOALGK 6 O

Smule 48 GGVFSVLKHTTWPTRKOSWHDFISILEYSAFFALVIFIFDKLLTL 61 GLAELLKRF

Smu1.968c GGSWLGKHALFILLKAGFKAYELAGAFEGWKGMHLPTEKC 62

Smule 72c GGLVMNDETIYLFTYENGOISYEEDKRDCSKNV 63

Smu2105 MRFLKDELSVSWRLOEKSIEALPFRTKIEIEIESDNOIKTL 64

Smu2106c GGASGEKILEKLIHERKCOLTONROIWLKTDLNNLMKDFYK 65

Smu2121c GGIILAKAADLAEIERIISEDPFKINEIANYDIIEFCPTKSSKAFEK 66

Uses of Targeting Moieties. indication of the presence and/or location, and/or quantity of the target (e.g., target microorganism). Thus targeting moi 0065. When exploited for their targeting activity, the novel eties are thus readily adapted for use in in vivo diagnostics, targeting peptides described herein (see, e.g., Table 2) can be and/or ex vivo assays. Moreover, because of Small size and used to preferentially or specifically deliver an effector to a good stability, the microorganism binding peptides are well microorganism (e.g., a bacterium, a fungus, a protozoan, a Suited for microassay systems (e.g., microfluidic assays (Lab yeast, an algae, etc.), to a bacterial film comprising the micro on a Chip), microarray assays, and the like). organism, to a biofilm comprising the microorganism, and the 0066. In certain embodiments the microorganism binding like. Where the effector comprises an epitope tag and/or a peptides (targeting peptides) can be attached to an effector detectable label, binding of the targeting moiety provides an that has antimicrobial activity (e.g., an antimicrobial peptide, US 2010/0316643 A1 Dec. 16, 2010

an antibacterial and/or antifungal, a vehicle that contains an 0072 These applications of microorganism binding pep antibacterial orantifungal, etc. In various embodiments these tides of this invention are intended to be illustrative and not chimeric moieties can be used in vivo, or ex vivo to prefer limiting. Using the teaching provided herein, other uses will entially inhibit or kill the target organism(s). be recognized by one of skill in the art. 0067. In certain embodiments the targeting peptides can be used in various pre-targeting protocols. In pre-targeting Uses of Antimicrobial Peptides. protocols, a chimeric molecule is utilized comprising a pri mary targeting species (e.g. a microorganism-binding pep (0073. When exploited for their antimicrobial activity, the tide) that specifically binds the desired target (e.g. a bacte novel antimicrobial peptides described herein (see, e.g., Table rium) and an effector that provides a binding site that is 2) can be used to inhibit the growth and/or proliferation of a available for binding by a Subsequently administered second microbial species and/or the growth or proliferation of a targeting species. Once Sufficient accretion of the primary biofilm comprising the microbial species. In various embodi targeting species (the chimeric molecule) is achieved, a sec ments the peptides can be formulated individually, in combi ond targeting species comprising (i) a diagnostic ortherapeu nation with each other, in combination with other antimicro tic agent and (ii) a second targeting moiety, that recognizes bial peptides, and/or in combination with various the available binding site of the primary targeting species, is antibacterial agents to provide antimicrobial reagents and/or administered. pharmaceuticals. 0068 An illustrative example of a pre-targeting protocol is the biotin-avidin system for administering a cytotoxic radio 0074. In various embodiments, the antimicrobial peptides nuclide to a tumor. In a typical procedure, a monoclonal described herein can be formulated individually, in combina antibody targeted against a tumor-associated antigen is con tion with each other, in combination with other antimicrobial jugated to avidin and administered to a patient who has a peptides, and/or in combination with various antibiotic (e.g., tumor recognized by the antibody. Then the therapeutic agent, antibacterial) agents in “home healthcare' formulations. e.g., a chelated radionuclide covalently bound to biotin, is Such formulations include, but are not limited to toothpaste, administered. The radionuclide, via its attached biotin is mouthwash, tooth whitening strips or Solutions, contact lens taken up by the antibody-avidin conjugate pretargeted at the storage, wetting, or cleaning Solutions, dental floss, tooth tumor. Examples of pre-targeting biotin/avidin protocols are picks, toothbrush bristles, oral sprays, oral lozenges, nasal described, for example, in Goodwin et al., U.S. Pat. No. sprays, aerosolizers for oral and/or nasal application, wound 4,863,713: Goodwin et al. (1988) J. Nucl. Med. 29: 226: dressings (e.g., bandages), and the like. Hnatowich et al. (1987).J. Nucl. Med. 28: 1294: Oehr et al. 0075. In various embodiments the antimicrobial peptides (1988).J. Nucl. Med. 29: 728; Klibanov et al. (1988).J. Nucl. described herein can be formulated individually, in combina Med. 29: 1951; Sinitsyn et al. (1989).J. Nucl. Med. 30: 66: tion with each other, in combination with other antimicrobial Kalofonos et al. (1990).J. Nucl. Med. 31: 1791; Schechter et peptides, and/or in combination with various antibiotic (e.g., al. (1991) Int. J. Cancer 48:167; Paganelli et al. (1991) Can antibacterial) agents in various cleaning and/or sterilization cer Res. 51: 5960; Paganelli et al. (1991) Nucl. Med. Com formulations for use in the home, workplace, clinic, or hos mun. 12: 211; Stickney et al. (1991) Cancer Res. 51: 6650: pital. and Yuan et al. (1991) Cancer Res. 51:3119. 0076. In certain embodiments the antimicrobial peptides 0069. It will be recognized that the tumor-specific anti described herein are attached to one or more targeting moi body used for cancer treatments can be replaced with a micro eties to specifically and/or to preferentially deliver the peptide organism binding peptide of the present invention and similar (s) to a target (e.g. a target microorganism, biofilm, bacterial pre-targeting strategies can be used to direct labels, antibiot film, particular tissue, etc.). ics, and the like to the target organism(s). 0077. Other possible uses of the targeting and/or antimi 0070 Three-step pre-targeting protocols in which a clear crobial peptides disclosed herein include, but are not limited ing agent is administered after the first targeting composition to biofilm dispersal, biofilm retention, biofilm formation, has localized at the target site also have been described. The anti-biofilm formation, cell agglutination, induction of motill clearing agent binds and removes circulating primary conju ity or change in motility type, chemoattractant or chemore gate which is not bound at the target site, and prevents circu pellent, extracellular signal for sporogenesis or other mor lating primary targeting species (antibody-avidin or conju phological change, induction or inhibition of virulence gene gate, for example) from interfering with the targeting of expression, utilized as extracellular scaffold, adhesin orbind active agent species (biotin-active agent conjugate) at the ing site, induction or suppression of host immune response, target site by competing for the binding sites on the active induction or Suppression of bacterial/fungal antimicrobial agent-conjugate. When antibody-avidin is used as the pri molecule production, quorum-sensing, induction of Swarm mary targeting moiety, excess circulating conjugate can be ing behavior, apoptosis or necrosis inducing in eukaryotic cleared by injecting a biotinylated polymer Such as biotiny cells, affecting control of or inducing the initiation of cell lated human serum albumin. This type of agent forms a high cycle in eukaryotes, in archaea or prokaryotes, induces molecular weight species with the circulating avidin-anti autolysis or programmed cell death, inhibition of phage?virus body conjugate which is quickly recognized by the hepato attachment or replication, evasion of innate immunity, induc biliary system and deposited primarily in the liver. tion or inhibition of genetic transformation or transduction 0071 Examples of these protocols are disclosed, e.g., in competence, induction or inhibition of pilus-mediated conju PCT Application No. WO 93/25240; Paganelli et al. (1991) gation, induction or inhibition of mating behavior in bacteria Nucl. Med. Comm., 12:211-234: Oehr et al. (1988).J. Nucl. and fungi, induction or inhibition of nodule formation or Med., 29: 728-729; Kalofonos et al. (1990).J. Nucl. Med., 31: metabolic compartmentalization, metal, ion, or nutrient bind 1791-1796; Goodwin et al. (1988) J. Nucl. Med., 29: 226 ing, acquisition or inhibition of metal, ion, or nutrient binding 234; and the like). and acquisition, and the like. US 2010/0316643 A1 Dec. 16, 2010

0078. These applications of the peptides described herein 0082 Targeting Moieties. are intended to be illustrative and not limiting. Using the I0083. In various embodiments this invention provides tar teaching provided herein, other uses will be recognized by geting moieties that preferentially and/or specifically bind to one of skill in the art. a microorganism (e.g., a bacterium, a fungus, a yeast, etc.). One or more such targeting moieties can be attached to one or Design and Construction of Chimeric Moieties. more effectors to provide chimeric moieties that are capable 0079. In various embodiments this invention provides chi of delivering the effector(s) to a target (e.g., a bacterium, a meric moieties comprising one or more targeting moieties fungus, a yeast, a biofilm comprising the bacterium or fungus attached to one or more effectors. The targeting moieties are or yeast, etc.). typically selected to preferentially bind to a target microor ganism (e.g., bacteria, Virus, fungi, yeast, alga, protozoan, I0084. In various embodiments, targeting moieties include, etc.), or group of microorganisms (e.g., gram-negative or but are not limited to peptides that preferentially bind particu gram-positive bacteria, particular genus, particular species, lar microorganisms (e.g., bacteria, fungi, yeasts, protozoa, etc.) In certain embodiments the targeting moiety comprises algae, viruses, etc.) or groups of Such microorganisms, anti one or more of the targeting peptides shown in Table 2, and/or bodies that bind particular microorganisms or groups of Table 4 and/or Table 6. In certain embodiments the targeting microorganisms, receptor ligands that bind particular micro moiety comprises non-peptide moieties (e.g., antibodies, organisms or groups of microorganisms, porphyrins (e.g., receptor, receptor ligand, lectin, and the like). metalloporphyrins), lectins that bind particular microorgan 0080. The effector typically comprises one or more moi isms or groups of microorganisms, and the like. As indicated, eties whose activity is to be delivered to the target microor it will be appreciated that references to microorganisms or ganism(s), and/or to a biofilm comprising the target microor groups of microorganism include bacteria or groups of bac ganism(s), and/or to a cell or tissue comprising the target teria, viruses or groups of viruses, yeasts or groups of yeasts, microorganism(s), and the like. In certain embodiments the protozoa or groups of protozoa, viruses or groups of viruses, targeting moiety comprises one or more antimicrobial pep and the like. tide(s) as described herein (see, e.g., antimicrobial peptides in 0085 Targeting Peptides. Table 2, and/or Table 8, and/or Table 9, and/or Table 10), an antibiotic (including, but not limited to a steroid antibiotic) 0086. In certain embodiments the chimeric constructs (see, e.g., Table 7), a detectable label, a porphyrin, a photo described herein comprise a targeting moiety that is or com sensitizing agent, an epitope tag, a lipid or liposome, a nano prises a targeting peptide. Typically the targeting peptides particle, a dendrimer, and the like. bind particular bacteria, and/or fungi, and/or yeasts, and/or 0081. In certain embodiments one or more targeting moi algae, and/or viruses and/or bind particular groups of bacte eties are attached to a single effector (see, e.g. FIG. 12). In ria, and/or groups of fungi, and/or groups of yeasts, and/or certain embodiments one or more effectors are attached to a groups of algae. The targeting peptides provided can be used single targeting moiety. In certain embodiments multiple tar to effectively deliver one or more effectors to or into a target geting moieties are attached to multiple effectors. The target microorganism. Illustrative targeting peptides include, but ing moiety(s) can be attached directly to the effector(s) or are not limited to the targeting peptides found in Table 2. through a linker. Where the targeting moiety and the effector I0087. Other suitable targeting peptides include the pep comprise peptides the chimeric moiety can be a fusion pro tides that have been identified as binding to particular target tein. organisms as shown in Table 4 and/or Table 4.

TABLE 3 Illustrative list of novel targetinct peptides.

SEO ID ID Target (s) Targeting Peptide Sequence NO

S initas YWNYNOSFNSGW 67

1T-2 initas NIFEYFILE 68 sanguinis gordonii mitis oralis - atypica Lactobacillus casei Saliva - derived biofilms

1T-3 initas WLGIAGGLDAYGELWGGN 69 s gordonii

1T-4 initas LDAYGELWGGN 70 gordonii sanguinis oralis atypica casei US 2010/0316643 A1 Dec. 16, 2010 12

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID D Target (s) Targeting Peptide Sequence NO

T- S. mutans GPIAGAAIGWDLGAISGAGL 71. S. sanguinis GWANFCO

T-6 S. mutans KFINGVLSOFVLERK 72

T-7 Myxococcus xanthus SORIIEPVKSPOPYPGFSVS 73

T-8 M. Xanthus FSWAACGEORAVTFWLLIEDLI 74

T-9 M. Xanthus WAWAESPRCWSTRSNIHALAF 7s RWEWAALT

T-1 O M. xanthus SPAGLPGDGDEA 76

T-11 S. mutans RISE 77 S. epidermidis P. aeruginosa

T-12 Corynebacterium FGNIFKGLKDWIETIWKWTAAK 78 xerosis Corynebacterium striatum S. epidermidis S. mutans

1T-13 S. aureus FRSPCINNNSLOPPGVYPAR 79 S. epidermidis P. aeruginosa

1T-14. S. mutans ALAGLAGLISGK 8O S. aureus S. epidermidis C. Xerosis

1T-15 S. militars DVILRVEAQ 81 1T-16 P. aeruginosa IDMR 82

1T-17 S. militars INNAIWYIS 83

1T-18 S. aureus YSKTLHFAD 84 S. epidermidis C. striatum P. aeruginosa

T-19 S. aires PGAFRNPOMPRG 85 S. epidermidis P. aeruginosa

T-2O S. militas PALWDLSNKEAWWAWLDDHS 86 P. aeruginosa

T-21 S. mutans YWEEAWRAALKKEARISTEDTP 87 P. aeruginosa WNLPSFDC

T-22 S. epidermidis WPLDDGTRRPEWARNRDKDRED 88 P. aeruginosa

T-23 S. militas PALWDLSNKEAWWAWLDDHS 89 P. aeruginosa

T-24 P. aeruginosa EEAEEKLAEWSQAVKRLVR 9 O

T-25 S. aires WGLDWSWLWLFFGLOLLSVILLG 91 S. epidermidis AMIR C. Xerosis C. striatum P. aeruginosa US 2010/0316643 A1 Dec. 16, 2010 13

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO

1T-26 S. militars LTILPTTFFAIIWPILAWAFIAYSG 92 S. aureus FKIKGIVEHKDOW S. epidermidis Corynebacterium lieikeium C. Xerosis C. striatum P. aeruginosa

1T-27 initas ALFWSLEOFLVVVAKSVFALCH 93 eS SGTLS epidermidis lieikeium xerosis striatum aeruginosa

1T-28 P. aeruginosa WSRDEAMEFIDREWTTLOPAG 94 KSHA

1T-29 initas GSWIKKRRKRMSKKKHRKMLR 95 eS RTRVORRKLGK epidermidis lieikeium xerosis striatum aeruginosa

1T-3 O eS GKAKPYOVROVLRAVDKLETR 96 epidermidis RKKGGR xerosis striatum aeruginosa

1T-31 initas NATGTDIGEWTLTLGRFS 97 i. aeruginosa

1T-32 S. initas WSFLAGWLCLGLAAWRLGNA 98

1T-33 eS VRTL TILVIFIFNYLKSISYKLKO 99 epidermidis PFENNLAOSMISI lieikeium xerosis striatum aeruginosa

1T-34 eS AFWLNILLTLLGYIPGIWHAWYI 1OO epidermidis IAKR lieikeium xerosis striatum aeruginosa

P. aeruginosa EICLTLWFPIRGSYSEAAKFPWPI 1O1 HIWEDGTWELPK

1T-36 eS WYRHLRFIDGKLWEIRLERK 1O2 epidermidis lieikeium xerosis striatum aeruginosa

1T-37 initas YIWGALWILAWAGLIYSMLRKA 103 eleS epidermidis lieikeium xerosis striatum aeruginosa US 2010/0316643 A1 Dec. 16, 2010 14

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID (s) Targeting Peptide Sequence NO

1T-38 initas WMFWLTRGRSPRPMIPAY 104 eleS epidermidis lieikeium xerosis striatum aeruginosa

1T-39 initas FGFCVWMYOLLAGPPGPPA 105 i. aeruginosa

1T - 4 O initas ORVSLWSEVEHEFR 106 i. aeruginosa

1T - 41 initas KRGSKIWIAIAWWLIWLAGWWWW 1. Of eS epidermidis lieikeium striatum aeruginosa

1T - 42 eS TWLDWISLALATGLFWYLLWA 108 epidermidis LLRADRA. xerosis striatum aeruginosa

1T - 43 C. jelikium DRCLSWLSWSPPKWSPLI 109 P. aeruginosa

1T-44 initas DPALADFAAGMRAQVRT 11 O eS epidermidis lieikeium striatum aeruginosa

1T-45 eS WTKPSFTDLRLGFEWTLYFANR 111 epidermidis striatum aeruginosa

1T-46 eS FSFKORVMFRKEVERLR 112 epidermidis lieikeium xerosis striatum aeruginosa

1T-47 initas WIKISWPGOVOMLIP 113 epidermidis aeruginosa

1T-48 eS KLOWHHGRATHTLLLQPPLCA 114 epidermidis PGTIR lieikeium xerosis striatum aeruginosa

1T - 49 eS SLVRIHDOOPWVTRGAFIDAAR 115 epidermidis TCS lieikeium : aeruginosa 1T-50 P. aeruginosa HSDEPIPNILFKSDSWH 116

S. eS GKPKRMPAEFIDGYGOALLAGA 117 aeruginosa US 2010/0316643 A1 Dec. 16, 2010 15

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO

1T-52 S. aureus DEYPAKLPLSDKGATEPRRH 118 C. Xerosis P aeruginosa

P. aeruginosa SDILAEMFEKGELOTLVKDAA 119 AKANA

1T-54 epidermidis RWVSCNPSWRIO 12 O xerosis striatum : aeruginosa xerosis NHKTLKEWKAKWGPEAVESW 21 aeruginosa ATLIG

T-56 C. xerosis LALIGAGIWMIRKG 22 P. aeruginosa T-57 P. aeruginosa RLEYRRLETOWEENPESGRRPM 23 RG T-58 P. aeruginosa CDDLHALERAGKLDALISA 24

eS AWGNNLGKDNDSGHRGKKHR 25 epidermidis KHKHR aeruginosa

eS YLTSLGLDAAEQAQGLLTILKG 26 epidermidis lieikeium striatum aeruginosa

1T - 61 P. aeruginosa HATLLPAVREAISROLLPALVP 127 RG

S. epidermidis GCKGCAORDPCAEPEPYFRLR 128 P. aeruginosa

1T - 63 eS EPLILKELWRNLFLFCYARALR 129 epidermidis lieikeium xerosis striatum aeruginosa

1T-64 eS OTWHHIHMHVLGOROMHWPPG 13 O epidermidis lieikeium xerosis striatum aeruginosa

1T - 65 initas HARAAWGWAELPROGAAWEWEL 131 eS IAAWRP epidermidis lieikeium xerosis striatum aeruginosa

1T - 66 initas DTDCLSRAYAORIDELDKOYA 132 eS GIDKPL epidermidis lieikeium xerosis striatum aeruginosa US 2010/0316643 A1 Dec. 16, 2010 16

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO

1T - 67 S. aires GORORLTCGRVSGCSEGPSREA 133 S. epidermidis AR C. jelikelium C. Xerosis C. striatum P. aeruginosa

1T - 68 S. militars GGTKEIWYORG 134 S. aureus C. jelikelium C. Xerosis C. striatum P. aeruginosa

T-69 S. militas ILSQEADRKKLF 35 P. aeruginosa

T-7 O S aires NROAOGERAHGEQOG 36 C. jelikelium P. aeruginosa T-71 P. aeruginosa KIDTNOWPPNKEG 37 T-72 P. aeruginosa EPTDGWACKER 38

T-73 Streptococcus GWWEELLHETILSKFKITKALE 39 pneumoniae LPIQL

T-74. S. pneumoniae DIDWGRKISCAAGWAYGAIDG 4 O CATTV

T-75 S. pneumoniae GVARGLOLGIKTRTOWGAATG 41 AA

T-76 S. pneumoniae EMRLSKFFRDFILWRKK 42 T-77 S. pneumoniae EMRISRIILDFLFLRKK 43 T-78 S. pneumoniae FFKTIFWLILGALGWAAGLYIEK 44 NYIDK

T-79 S. pneumoniae FGTPWSITNEWKKNFNDRPDF 45 DSDRRRY

T-80 S. pneumoniae GGNLGPGFGWIIP 46 T-81 S. pneumoniae AIATGLDIWDGKFDGYLWA 47 T-82 S. pneumoniae FGWGWGIALFMAGYAIGKDLR 48 KKFGKSC

T-83 S. pneumoniae OKPRKNETFIGYIORYDIDGNG 49 YOSLPCPON T-84 S. pneumoniae FRKKRYGLSILLWLNAFTNLWN SO SIHAFYMTLF

T-85 A. naeslundii, F. nucleatum, WMASLTWRMRAASASLPTHSR 51 P. gingivalis TDA S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-86 S. mitis, S. oralis, S. salivarious HRKNPWLGWGRRHRAHNWA 152 1T-87 S. mitis, S. mutans, S. oralis EAVGODLVDAHHP 153 1T-88 Unanalyzed GRLWLEITADEWKALGEALAN 154 AKI US 2010/0316643 A1 Dec. 16, 2010 17

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID Target (s) Targeting Peptide Sequence NO S. mitis, S. mutans HEDDKRRGMSVEVLGFEVWOH 55 EE

gordonii, S. mitis, S. mutans, RNVIGOVL 56 oralis, S. sanguinis

mitis, S. mutans, S. oralis, TSWRPGAAGAAWPAGAAGAA f sanguinis GAGWRWP

mitis, S. mutans GODEGORRAGWGEGQGWDG 58

epidermidis, S. gordonii, AMRSVNOA 59 mitis, S. mutans, oralis, S. sanguinis

mitis, S. mutans, S. oralis DOVAHSGDMLVOARRRDS 6 O

gordonii, S. mitis, S. mutans, 61 oralis, S. sanguinis

gordonii, S. mitis, S. mutans, WAGACAQPFGGO 62 s oralis, S. sanguinis naeslundii, F. nucleatum, GWAERNLDRITWAWAIIWTITIW 63 gingival is GIGLWAKLG epidermidis, gordonii, S. mitis, S. mutans, oralis S. salivarious sanguinis

1T-98 naeslundii, F. nucleatum, WRSAKAWKALTAAGYTGELWN 164 gingival is WSGGMKAWLGO epidermidis, gordonii, S. mitis, S. mutans, oralis, S. salivarious, sanguinis

1T-99 gordonii, S. mitis, S. mutans, MKAWLGO 1.65 s oralis, S. sanguinis 1T-1 OO S. gordonii, S. mitis, S. mutans LDPLEPRIAPPGDRSHOGAPAC 166 HRDPLRGRSARDAER

1T-101 naeslundii, P. gingivalis RLRWGRATDLPLTSFAWGVWR 167 epidermidis, NLPDAPAH gordonii, S. mitis, S. mutans, : oralis, S. sanguinis 1T-102 naeslundii, F. nucleatum, WKRLWPARILAGHSRRRMRW 168 gingival is MWWWRYFAAT epidermidis, gordonii, S. mitis, S. mutans, oralis, S. salivarious, sanguinis

1T-103 naeslundii, F. nucleatum, AQFYEAIITGYALGAGORIGOL 169 gingival is epidermidis, gordonii, S. mitis, S. mutans, oralis, S. sanguinis

1T-104 mitis RAVAAHLQGRHHGHQWRROR 17 O HGOR

1T-105 epidermidis, S. gordonii, GEGLPPPWLHLPPPRMSGR 171 mitis, S. mutans, s oralis 1T-106 gordonii, S. mitis, S. mutans, DALRRSRSOGRRHR 172 oralis, S. salivarious US 2010/0316643 A1 Dec. 16, 2010 18

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-1. Of A. naeslundiis. epidermidis, SPWPRFTAWGGWSRGSP 173 S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-108 S. gordonii, S. mitis, S. mutans, WGPLGPERPLW. 174 S. oralis, S. salivarious, S. sanguinis

1T-109 A. naeslundiis. epidermidis, WTTNVROGAGS 17s S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-110 A. naeslundii, P. gingivalis LAAKTAWCWGRAFM 176 S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-111 A. naeslundii, F. nucleatum, GRLSRREEDPATSIILLRGAYR 177 P. gingivalis MAWF S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-112 S. gordonii SDNDGKLILGTSQ 178

1T-113 S. mitis HGAHORTGORLHHHRGRTVSG 179 CRONPVAGVDPDEHR

1T-114 A. naeslundii, P. gingivalis ROAPGPGLVTITAACSAPGSRSR 18O S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-115 A. naeslundii, F. nucleatum, LLIERFSNHH 181 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-116 A. naeslundii, P. gingivalis MILHRRRDR 182 S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-117 S. mutans GPGWWGPAPFSRLPAHALNL 183

1T-118 A. naeslundii, F. nucleatum, TASPPAPSDQGLRTAFPATLLIA 184 P. gingivalis LAALARISR S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-119 S. gordonii, S. mitis, S. mutans, SPATOKAPTRAOPSRAPVODC 185 S. oralis GDGRPTAAPDDWERLSPR

1T-120 A. naeslundii, F. nucleatum, DWRDRWDLAGADLCAAHATR 186 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-121 S. gordonii, S. mitis, S. mutans, FAKETGFGIGGAQEGWWIIADI 187 S. oralis, S. salivarious, YGPNPF S. sanguinis US 2010/0316643 A1 Dec. 16, 2010 19

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID Target (s) Targeting Peptide Sequence NO

T-122 S. mitis GAIPDPWTHRVDWEEDHOTRP 188 SR

T-123 S. gordonii LVRRNAVAGRSDGLAGAEOLD 189 LVRLQGVL

T-124 S. mitis, S. mutans, S. oralis LFDERNKIA 19 O

T-125 S. epidermidis, S. gordonii, DAITGGNPPLSDTDGLRP 191 S. mutans, S. oralis

T-126 S. gordonii, S. mitis, S. mutans OGLARPWLRRIPL 192

T-127 A. naeslundii, F. nucleatum, YDPWPKRKNKNSEGKREE 193 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-128 A. naeslundii, P. gingivalis SGSAIRMLEIATKMLKR 194 S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-129 A. naeslundii, P. gingivalis YDKYIKYLSIOPPFIWYFI 195 S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-130 A. naeslundii, F. nucleatum, OKIIDMSKFLPSLILFIMIVWIYI 196 P. gingivalis GKSIGGYSAIWSSIMLELDTWLY S. epidermidis, NKKIFFIYK S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-131 A. naeslundii, F. nucleatum, DEWWKMLGI 197 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-132 A. naeslundii, F. nucleatum, YSKKLFEYFYFIIFILIRYLIFYKI 198 P. gingivalis IONKNYYINNIAYN S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-133 A. naeslundii, P. gingivalis YFIKDDNEALSKDWEWIGNDL 199 S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-134 A. naeslundii, F. nucleatum, SRLWREIKKKCRKS 2OO P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-135 A. naeslundii, P. gingivalis FESLLPOATKKIVNNKGSKINKIF S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis US 2010/0316643 A1 Dec. 16, 2010 20

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-136 A. naeslundii, F. nucleatum, ELLTOIRLALLYSWNEW P. gingivalis, S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-137 A. naeslundii, F. nucleatum, PLNFYRAWKENRLPLSEKNIND P. gingivalis FTNIKLKVSPKLINLLOESSIFY S. epidermidis, NFSPKKRNTN S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-138 A. naeslundii, F. nucleatum, YPNEYCIFLENLSLEELKEIKAI 2O4. P. gingivalis NGETLNLEEIINERKNLKD S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-139 A. naeslundiiS. gordonii, AWAGAAWGALLGNDARSTAW 2O5 S. mitis, S. mutans, S. oralis GAAIGGAL.GAGAGELTKNK

1T-14 O A. naeslundii, F. nucleatum, IKGTIAFWGEDYWEIRWDKGWK P. gingivalis LTFRKSAIANVINNNOO S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-141 F. nucleatum, P. gingivalis KKFIILLFILVOGLIFSATKTLSD S. epidermidis, IIAL S. gordonii, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-142 A. naeslundii, F. nucleatum, FTOGIKRIVLKRLKED P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-143 A. naeslundii, F. nucleatum, MPKRHYYKLEAKALOFGLPFA 209 P. gingivalis YSPIOLLK S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-144 A. naeslundii, F. nucleatum, IIELHPKSWTODWRCSFL 21 O P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-145 S. mitis, S. mutans, S. oralis WEAGKRNISLENIEKISKGLGISI 211 SELFKYIEEGEDKIG

1T-146 A. naeslundii, F. nucleatum, RNSADNOTKIDKIRIDISLWDE 212 P. gingivalis, HLNIWKOGK T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-147 A. naeslundii, F. nucleatum, GWENRRFYERDWSKWSMMTSE 213 P. gingivalis, AWAPRGGSK T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis US 2010/0316643 A1 Dec. 16, 2010 21

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-148 A. naeslundii, F. nucleatum, IWELDDTTILERALISMILGEANA 214 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-149 A. naeslundii, F. nucleatum, SWRAWKPIDETWARHFPGDFIWN 215 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-150 A. naeslundii, F. nucleatum, YINRRLKKAFSDADIKEAPAEF 216 P. gingivalis, YEELRRVOYV T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-151 A. naeslundii, F. nucleatum, SWRAWKPIDEIWAWHFPGDFIWN 217 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-152 A. naeslundii, F. nucleatum, YWSADESAYNHIWTDDIPLADR 218 P. gingivalis RIEAVOO S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-153 A. naeslundii, F. nucleatum, YIACPGYFY 219 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-154 P. gingivalis YFSFLEIWGMARR 22 O

1T-155 A. naeslundii, F. nucleatum, LKLAFGVYPFOAMSOSDTAVS 221 P. gingivalis ERNWLWR S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-156 A. naeslundii, F. nucleatum, GRFOISIRGEEKSKWKVOGKGT 222 P. gingivalis, FTDRNTT T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-157 A. naeslundii, F. nucleatum, RRFRKTTENREKSKNKKAWLG 223 P. gingivalis, LSTTSTASY T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-158 A. naeslundii, F. nucleatum, WENKPSPLGSIKKLQGLWYRLI 224 P. gingivalis GYRHFWW S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-15.9 P. gingivalis IFSLHHFALICSEMGTFAWSKRA 225 KYKWEWL US 2010/0316643 A1 Dec. 16, 2010 22

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-160 A. naeslundii, F. nucleatum, AQYKYINKLLN 226 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-161. A. naeslundii, F. nucleatum, NKVLOVEVMWDGSVVGRPAG 227 P. gingivalis WISIKSSKKG S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-162 A. naeslundii, F. nucleatum, OKAKEESDRKAAVSYNGFHRV 228 P. gingivalis, NWWSIPK T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-163 A. naeslundii, F. nucleatum, MENILIYIPMWLSPFGSGILLFLG 229 P. gingivalis KDRRYML S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-164 A. naeslundii, F. nucleatum, KKSHSOGKRKLKDLNSAYKID 23 O P. gingivalis NQLHYALR S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-16.5 A. naeslundii, F. nucleatum, CYDSFDFSIFWTFANRMIKLSWGS 231 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-166 A. naeslundii, F. nucleatum, AOSAGOIKRKSKVRIHV 232 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-167 A. naeslundii, F. nucleatum, SRMSEHSPAGLWFEWGPMDKG 233 P. gingivalis SFIILDSYHPTWKK S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-168 A. naeslundii, F. nucleatum, ELHRIMSTEKIGAWTKMNFDTA 234 P. gingivalis PIMSILPIDIYPKEWGIGS S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-169 A. naeslundii, F. nucleatum, FARVRRLHONRILTOPLTNLKY 235 P. gingivalis CLROPIYSD S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-170 P. gingivalis AYGKWFSMDIMLSENDKLIWLR 236 ISHHSAWH US 2010/0316643 A1 Dec. 16, 2010 23

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-171 A. naeslundii, F. nucleatum, SWRAWKPIDKTWARHFPGDFIWN 237 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-172 A. naeslundii, F. nucleatum, FEGLKNLLGDDII 238 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-173 A. naeslundii, F. nucleatum, LFRKEDOEHVLL 239 P. gingivalis S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis 1T-174 A. naeslundii, F. nucleatum, SGGSDTDGSSSGEPGSHSGDL 24 O P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis 1T-175 A. naeslundii, F. nucleatum, GEPGSHSGDL 241 P. gingivalis, S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis 1T-176 A. naeslundii, P. gingivalis PWGDIMSGFLRGANOPRFLLDH 242 S. epidermidis, ISFGS S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis 1T-177 P. gingivalis.S. gordonii, GTNWPTOILGYSREERFDYEPA 243 S. mitis, S. mutans, S. oralis, PEOR S. salivarious, S. sanguinis 1T-178 A. naeslundii, F. nucleatum, LLASHPERISLGWFFWYRWLHL 244 P. gingivalis LLENT S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-179 A. naeslundii, F. nucleatum, TCYPLIORKTDRAYEA 245 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis 1T-180 A. naeslundii, F. nucleatum, WWFGGGDRLW 246 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis 1T-181 A. naeslundii, F. nucleatum, YGKESDP 247 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis 1T-182 A. naeslundii, F. nucleatum, LTASICROWNDNSTPYOR 248 P. gingivalis, T. denticolas gordonii, US 2010/0316643 A1 Dec. 16, 2010 24

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-183 A. naeslundii, F. nucleatum, PLRSFWAEKAEHAFRVWRIADF 249 P. gingivaliss. DFGHS epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-184 A. naeslundii, F. nucleatum, ALLVLNLLLMOFFFGKNM 25 O P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-185 A. naeslundii, F. nucleatum, HYHFLLEFGFHKGDYLE 251 P. gingivalis, T. denticolas gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-186 S. sanguinis LAKKNOALREEISROKSK 252

1T-187 S. sanguinis RAGRIKKLSOKEAEPFEN 253

1T-188 S. sanguinis HRKDWYKK 254

1T-189 F. nucleatum, S. sanguinis FIRSKLRRWDFSGWRRGNKHFL 255 LDKLLITLWK

1T-190 A. naeslundii, F. nucleatum, IOIIVNAFVEKDKTGAVIEWLYA 256 P. gingivaliss. SNNHEKWKAKYEELWAIS epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

F. nucleatum, S. sanguinis SALFYDTLAAIWISIAGWDARW 257 GH

S. sanguinis ILWLLALOWELDSKFOY 258

S. sanguinis LMIFDKHANLKYKYGNRSFGW 259 EAIM

F. nucleatum, S. sanguinis LAGATLWTPYCWGWGLIRSH 26 O Unanalyzed AASGFTYCASNGWWHPY 261

F. nucleatum, S. sanguinis KPEKEKLDTNTLMKWWNKALS 262 LFDRILLIKFGA.

A. naeslundii, F. nucleatum, TEILNFLITWCADRENWKIKHG 263 P. gingivaliss. LSDSWLLIFFARFTGAEYW epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-198 P. gingivaliss. MPWSKKRYMLSSAYATALGIC 264 epidermidis, S. gordonii, YGOVATDEKESEITAIPDLLDY S. mitis, S. mutans, S. oralis, LSWEEYLL S. sanguinis

1T-199 S. sanguinis RAGRIKKLSOKEAEPFEN 265 1T-2OO A. naeslundii, F. nucleatums. MRFKRFDRDYALSGDNWFEWL 266 epidermidis, S. gordonii, TASCDVIERNLSYREMCGLMO S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis US 2010/0316643 A1 Dec. 16, 2010 25

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO

S. sanguinis KRKHENWIWAEEMRWIKN 267

A. naeslundii, F. nucleatum, LCRLEKLCKOFLRODKVVTYY 268 P. gingivaliss. LMLPYKRAIEAFYOELKERS epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

A. naeslundii, F. nucleatum, YPFCLATWDHLPEGLSWTDYER 269 P. gingivaliss. WORLWSOFLLNKEER epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

F. nucleatum, S. sanguinis KYLFLASKTKEYFKSHFREIMI 27 O DV

A. naeslundii, F. nucleatum, FISFWDCIONIEKIEKELLKIGIT 271 P. gingivaliss. DIOINQDAGWLY epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

S. sanguinis AGFAAGYSL 272 F. nucleatum, S. sanguinis SPLEKYGTGSMTALTFLLGCCL 273 LWLSKKSR

Unanalyzed KRKRWAILTLFLAGLGAWGIWL 274 ATF

T-209 F. nucleatum, S. sanguinis WSGAAWGAATFC 27s S. sanguinis SVGMGVIERGSFDFSASAILOK 276 RETKCLKNKPFT

S. sanguinis AEPIIKWTEG 277

S. sanguinis LLSALIKKLALIIFIG 278

S. sanguinis AYLLTCAAAGGMIGYGAATLD 279

S. sanguinis MIGYGAATLD 28O

S. sanguinis WCFKDISVFLSPFRGOEWLFCG 281 KAKHSLIYWIGT

S. sanguinis FFLNWIAIRIPHF 282

F. nucleatum, S. sanguinis MLSNWLSRSWWSPNWDIPNSMW 283 ILSPLLISISNYH

F. nucleatum, S. sanguinis KLIFAALGLWFLLIGLRDSRSK 284

S. sanguinis RNINWSATFITEKSLW 285

A. naeslundii, F. nucleatum, AILTFFMALLFTYLKEKAOILY 286 P. gingivaliss. WPLFLHLMFYFWTA epidermidis, S. gordonii, S. oralis, S. salivarious, S. sanguinis

1T-221 A. naeslundii, F. nucleatum, DIGRIIGKKGRTITAIRSIWYSWP 287 P. gingivaliss. TOGKKVRLVIDEK epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis US 2010/0316643 A1 Dec. 16, 2010 26

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-222 F. nucleatum, S. sanguinis RIEASLISAIMFSMFNAIVKFLOK 288

1T-223 A. naeslundii, F. nucleatum, NOKMEINSMTSEKEKMLAGHF 289 P. gingivaliss. HNEANFAWIFKYSLFYNFF epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-224 A. naeslundii, F. nucleatum, WHLFSFWKLIYYDIMKYSIEEK 29 O P. gingivaliss. WFFESPWGEIIQ epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-225 A. naeslundii, F. nucleatum, RRSLGNSASFAEWIEYIRYLHYI 291 P. gingivaliss. IRVOFIHFFSKNKKI epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-226 A. naeslundii, F. nucleatums. KLOEKOIDRNFERVSGYSTYRA 292 epidermidis, WOAAKAKEKGFISLEN S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-227 S. sanguinis RFEOFFADHYPFW 293

1T-228 A. naeslundii, F. nucleatum, IFKLFEEHILLYLLDAFYYSKIFR 294 P. gingivaliss. RLKOGLYRRKEOPYTODLFRM epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-229 S. gordonii, S. oralis, S. sanguinis LLINYWKWNMSY 295

1T-23 O A. naeslundii, F. nucleatum, EFLEKFKVLKOPRKANNISKNR 296 P. gingivaliss. WAMIFLTIHKSRGFLSSPY epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-231 S. gordonii, S. mitis, S. mutans, FDFLCSPDSSR 297 S. oralis, S. salivarious

1T-232 S. sanguinis AYSLTFONPNDNLTDEEVAKY 298 MEKITKALTEKIGAEWR

1T-233 A. naeslundii, P. gingivaliss. TDOELEHLIVTELESKRLDFTYS 299 epidermidis, KDITEFFDEAFPEYDONY S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-234 A. naeslundii, F. nucleatum, DNFYLILKMEERGKSKKTSOTR P. gingivaliss. GFRAFFDIIRKKIKKEDGK epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-235 S. sanguinis GWLSDDFWLKSAIPLLKKRLA. 3O1 KWNETL US 2010/0316643 A1 Dec. 16, 2010 27

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-236 A. naeslundii, F. nucleatum, PVOKALHVVSAYATDLGICYD 3O2 P. gingivaliss. OVWTVMIREVKTOLYOIY epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-237 S. sanguinis EDPWPNHFTLRRNKKEKPSKS

1T-238 A. naeslundii, F. nucleatum, IFNRRKFFOYFGLSKEAMVEHI P. gingivaliss. QPFILDIWOIHLF epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-239 A. naeslundiiS. gordonii, ADDLLNKRLTDLIMENAETWK 305 S. mitis, S. mutans, S. oralis, TIDLDNSD S. sanguinis

1T-24 O A. naeslundii, F. nucleatum, WILGNGISNIAQTLGOLPNIAW 3 O 6 P. gingivaliss. WWIYMWLIAALLEESNWC epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-241 S. sanguinis TOKTYLHIIRELENODIDLIMRS 3. Of LTSLT

1T-242 F. nucleatum, S. sanguinis KOVONTTLIICGTVLLGILFKSY LKSQKSW

1T-243 A. naeslundii, P. gingivaliss. SENIARFAAAFENEOVWSYAR 309 epidermidis, WFRRSWRGSGSSSRF S. gordonii, S. mitis, S. mutants, S. oralis, S. salivarious, S. sanguinis

1T-244 A. naeslundii, P. gingivalis MTWAEIGAIWGATIGSFYIPNPW 31 O S. epidermidis, IWPFRVR S. gordonii, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-245 F. nucleatum, S. sanguinis IIGGISGAGWGIASFC 311

1T-246 S. sanguinis ISGAGWGIASFC 312

1T-247 A. naeslundii, F. nucleatum, LSISORTDRVIVMDKGKIIEEGT 313 P. gingivalis HSELIAANGFYHHLFNK S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-248 S. sanguinis IGGALNSCG 314

1T-249 F. nucleatum, S. sanguinis WFSVLKHTTWPTRKOSWHDFIS 315 ILEYSAFFALWIFIFDKLLTLGLA ELLKRF

1T-250 S. mitis, S. mutans, S. oralis LVOGDTILIENHVGTPVKDDGK 316 DCLIIREADWLAWWND

1T-251 S. mitis, S. oralis, S. sanguinis LVMNDETIYLFTYENGOISYEE 317 DKRDCSKNW

1T-252 F. nucleatum, S. sanguinis MKKNLKRFYALWLGFIIGCLFW 3.18 SILIFIGY US 2010/0316643 A1 Dec. 16, 2010 28

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-253 A. naeslundii, F. nucleatum, KTKESLTOOEKKFLKDYDRKS 319 P. gingivalis LHHFRDILTYCFILDKLTNK S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-254 S. sanguinis RFLKDELSVSWRLOEKSIEALPF RTKIEIEIESDNOIKTL

1T-255 A. naeslundii, F. nucleatum, LFIWEYKDKASWPGEIDNTYWE 321 P. gingivalis SYTYSDILTEKTLIRYFD S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-256 S. sanguinis KGKSLMPLLKOINQWGKLYL 322

1T-27 A. naeslundii, F. nucleatum, IILAKAADLAEIERIISEDPFKIN 323 P. gingivalis EIANYDIIEFCPTKSSKAFEKWLK S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-258 A. naeslundii, F. nucleatum, TINIDDKWLDYLKKINSKAITID 324 P. gingivalis, LIGCAS T. denticola, S. mitis, S. mutans, S. oralis

1T-259 F. nucleatum, P. gingivalis, EKLKKILLKLAWCGKAWYTL 3.25 T. denticola, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-260 A. naeslundii, P. gingivalis NILYFIHDENOWEPOKAEIFRG 326 S. epidermidis, SIKHCAWLSS S. gordonii, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-261 F. nucleatum S. mutans, SFEKNKIENNLKIAQAYIYIKPK 327 S. oralis S. sanguinis PRICOA

1T-262 A. naeslundii, F. nucleatum, LSLPLIWLTKSI 328 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-263 A. naeslundii, F. nucleatum, FIAWSFTGNPATFKLWIGCKADN 329 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. oralis, S. salivarious, S. sanguinis

1T-264 S. sanguinis LEGKFYMAEDFDKTPECFKDYW 33 O

1T-265 A. naeslundii, F. nucleatum, GMFENLLMINFOIMNDLKIEIV 331 P. gingivalis WKDRICAW S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-266 S. sanguinis RAGTWLWWDEIR 332 US 2010/0316643 A1 Dec. 16, 2010 29

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO 1T-267 A. naeslundii, F. nucleatum, RIKEERKNRSYKFFIWRLFDEK 333 P. gingivalis, TGFI T. denticola, S. mitis, S. mutans, S. oralis S. sanguinis

1T-268 F. nucleatum S. mutans, PITPKKEKCGLGTYAPKNPWFS 334 S. oralis S. sanguinis KSRW

1T-269 F. nucleatum S. mutans, PLYWAAWEKINTAKKH 335 S. oralis S. sanguinis

1T-270 F. nucleatum S. mutans, WHEFDIOKILONR 336 S. oralis S. sanguinis

1T-271 A. naeslundii, F. nucleatum, FLIOKFLLIKTFPPYRKKYWWIV 337 P. gingivalis SOTGTA S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-272 F. nucleatum S. mutans, QL.APIDKOLKAVKKIAFYESES 338 S. oralis S. sanguinis TAAKAWTWA

1T-273 F. nucleatum, P. gingivalis, YNEPNYKWLESYKIYKORCED 339 T. denticola, RTGMYYTEET S. mitis, S. mutans, S. oralis

1T-274 F. nucleatum S. mutans, ETTTEINAIKLHRIKORSPOGTR 34 O S. oralis S. sanguinis RVN

A. naeslundii, F. nucleatum, OVLKNFSISRRYKINNPFFKILL 341 P. gingivalis, FIOLRTL T. denticola, S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-276 A. naeslundii, F. nucleatum, ILTLLILGSIGFFILKIKLKLGRF 342 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-277 A. naeslundii, F. nucleatum, IYYMRFWNKPLEKTFFK 343 P. gingivalis, T. denticola S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-278 A. naeslundii, F. nucleatum, SINSSAGIOPHCLSSSFVLRTKH 344 P. gingivalis, CFY S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-279 A. naeslundii, F. nucleatum, 345 P. gingivalis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

A. naeslundii, F. nucleatum, TNNKNKWIIKAIKFKNKDFINL 346 P. gingivalis, DLFIYRR T. denticola S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-281 A. naeslundii, F. nucleatum, KYEKLTKENLFIRNSGNMCWFI 347 P. gingivalis YFLFFG S. epidermidis, US 2010/0316643 A1 Dec. 16, 2010 30

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-282 F. nucleatum, P. gingivalis, ISLWFPAYT 348 S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-283 A. naeslundii, F. nucleatum, LCTKLEDKORGRIPAELFIISPIK 349 P. gingivalis, ILERNDAL T. denticola, S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-284 A. naeslundii, F. nucleatum, 350 P. gingivalis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-285 A. naeslundii, F. nucleatum, FFPYYLADFYKOLKFLNEYOT 351 P. gingivalis, KNKDKWWEFK S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-286 S. sanguinis LGFFNNKADLWKADTERDNRM 352 SSLKIKDL

1T-287 P. gingivalis, T. denticola KGYPLPFOYRLNNH 353 S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-288 F. nucleatum, S. gordonii, RWWGGEPSADIYLSAKDTKT 3.54 S. salivarious, S. sanguinis

1T-289 F. nucleatum, P. gingivalis, EPSADIYLSAKDTKT 355 S. gordonii, S. mitis, S. mutans, S. oralis, S. sanguinis

1T-290 A. naeslundii, F. nucleatum, IINOLNLILLRLMEILIL 356 P. gingivalis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-291 A. naeslundii, F. nucleatum, DMKIIKLYIKILSFLFIKYCNKK 357 P. gingivalis, LNSWKLKA. T. denticola, S. mitis, S. mutans, S. oralis

1T-292 A. naeslundii, F. nucleatum, IINOLNLILLRLMEILIL 358 P. gingivalis S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-293 A. naeslundii, F. nucleatum, HWEDCFLLSNARTTAIHGRANP 359 P. gingivalis ARGEPRTRSE S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-294 T. denticola 360 US 2010/0316643 A1 Dec. 16, 2010 31

TABLE 3 - continued Illustrative list of novel targeting peptides. SEO ID ID Target (s) Targeting Peptide Sequence NO

1T-295 S. mitis, S. salivarious, KYKLKKIIL 361 S. sanguinis

1T-296 A. naeslundii, F. nucleatum, EYSOOSFKAKPCSERGVLSP 362 P. gingivalis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-297 A. naeslundii, F. nucleatum, RSLRLNNALTKLPKLWYNRIKE 363 T. denticola, AFYAYNDYDK S. mitis, S. mutans, S. oralis

1T-298 A. naeslundii, F. nucleatum, 364 P. gingivalis, T. denticola S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-299 A. naeslundii, F. nucleatum SMLTSFLRSKNTRSLKMYKDW 365 S. epidermidis, HF S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

A. naeslundii, F. nucleatum, PLIISKAQIKMSGDILGSCFKLF 366 P. gingivalis YLRPFF S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-301 F. nucleatum, S. gordonii, SKLPRWLDASLKL 367 S. sanguinis

A. naeslundii, P. gingivalis IIILPKIYLWCKTV 368 S. epidermidis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

1T-303 A. naeslundii, F. nucleatum, LDYENMDCKKRIRI 369 P. gingivalis, S. gordonii, S. mitis, S. mutans, S. oralis, S. salivarious, S. sanguinis

T-304 P. gingivalis STAGEASRRTASEASRRTAAKL 37 O RG

-3 OS F. nucleatum ARNALNMRDWPWDAAIIGIIDG 3.71 MDEE

F. nucleatum KILNEAEGKLLKWIEKNGEIDIE 372 EI

-3 Of F. nucleatum NGDKKAKEELDKWDEWIKELN 373 IOF

F. nucleatum GLVIIPNLIALIILFSQWROQTKD 374 YFSNPKLSSR

F. nucleatum EPLPLTKYDKKDTEMKKWFKEI 375 LAGKWGYEKEEE

T-310 F. nucleatum TKLKKNNKLLSAKKENTLHTK 376 DK

- 311 S. mutans, S. sobrinus AIFDAMHNL 377 US 2010/0316643 A1 Dec. 16, 2010 32

0088. As described above, in certain embodiments of the display peptide library can be screened against a target micro present invention, the targeting moiety can comprise target ing peptide capable of binding, specifically binding, or pref bial organism or a desired antigen or epitope thereof. Any erentially binding to a microorganism, e.g., a target microbial peptide identified through Such screening can be used as a organism. In one embodiment, the targeting peptide be iden targeting peptide for the target microbial organism. Illustra tified via screening peptide libraries. For example, a phage tive additional targeting peptides are shown in Table 4.

TABLE 4 Additional illustrative targeting moieties. Targeting Moiety/ SEO ID Organism Structure/sequence NO

LPSB-1 RGLRRLGRRGLRRLGR 378

Phoo-1 KPWLPWLPWLPWL 379

LPSB-2 WLRIIRIAWLRIIRIA 38O

LPTG-1 LPETGGSGGSLPETG 381

C-1 RAHIRRAHIRR 382

ANION-1 DEDEDDEEDDDEEE 383

PHILIC-1 STMCGSTMCGSTMCG 384

SA5. 1/S. aureus WRLPLWLPSLNE 385

SA5.3/S. aureus ANYFLPPWLSSS 386

SA5.4/S. aureus SHPWNAORELSV 387 SA5.5/S. aureus SWSWGMRPMPRP 388

SA5.6/S. aureus WTPLHPSTNRPP 389

SA5.7/S. aureus SWSWGMKPSPRP 390

SA5.8/S. aureus SWSWGMKPSPRP 391

SA5.9/S. aureus SVPWGPYNESOP 392 SA5. 10/S. aureus WAPPLFRSSLFY 393

SA2.2/S. aureus WAPPXPXSSLFY 394

SA2.4/S. aureus HHGWTHHWPPPP 395

SA2.5/S. aureus SYYSLPPIFHIP 396 SA2.6/S. aureus HFOENPLSRGGEL 397 SA2.7/S. aureus FSYSPTRAPLNM 398

SA2.8/S. aureus SXPXXMKXSXXX 399

SA2.9/S. aureus WSRHOSWHPHDL 4 OO SA2.10/S. aureus DYXYRGLPRXET 4O1

SA2.11/ S. aureus SWSWGMKPSPRP 4 O2

S. aureus/Consensus WAQAH-PAH-H-E-FAY-K/H-HA-LAH-X-X-K/R-PAL 4 O3 DH5.1/E. coli KHLONRSTGYET 4O4.

DH5.2/E. coli HIHSLSPSKTWP 4 OS

DH5.3/E. coli TITPTDAEMPL 4O6

DH5.4/E. coli HLLESGWLERGM 4. Of

DH5.5/E. coli HDRYHIPPLOLH 408

DH5.6/E. coli WNTLONVRHMAA 409 US 2010/0316643 A1 Dec. 16, 2010 33

TABLE 4 - continued Additional illustrative targeting moieties. Targeting Moiety/ SEQ ID Organism Structure/sequence NO

DH5.7/E. coli SNYMIKLRAWSPF DH5.8/E. coli NLOMPYAWRTEF DH5.9/E. coli OKPLTGPHFSLI CSPAS. mutans SGSLSTFFRLFNRSFTOALGK CSPC18/S. mutans LSTFFRLFNRSFTOALGK CSPC16/S. mutans TFFRLFNRSFTOALGK

CSPM8AS. mutans TFFRLFNR KH/Pseudomonas spp KKHRKHRKHRKH (US 2004/O 137482) cCF10

AgrD1 YSTCDFIM

AgrD2 GWNACSSLF

AgrD3 YINCDFLL 421

Nisina ITSISLCTPGCKTGALMGCNMRTATCIICSIIIWSK 422

PlnA. KSSAYSLOMGATAIKQWKKLFKKWGW 423

S3L1-5 WWYNWWODW 424

Penetratin 425

Tat EHWSYCDLRPG 426

Pep-1N KETWWETWWTEW 427

Pep27 MRKEFHNWLSSGOLLADKRPARDYNRK 428

HABP35 429

HABP42 (all D) STMMSRSHKTRSHHW 43 O

HABPS2 GAHWQFNALTWRGGGS 431

Hi3/17 KORTSIRATEGCLPS 432

C.-E. coli peptide QEKIRVRLSA 433

Salivary Receptor OLKTADLPAGRDETTSFWLV* 434 Adhesion Fragment

S1 (Sushi frag.) GFKLKGMARISCLPNGOWSNFPPKCIRECAMVSS 435 (LPS binding)

S3 (Sushi frag.) HAEHKWKIGWEOKYCOFPOGTEVTYTCSGNYFLM 436 (LPS binding)

MArg. 1 AMDMYSIEDRYFGGYAPEWG 437 (Mycoplasma infected cell line binding peptide

BPI fragment 1 ASQQGTAALOKELKRIKPDYSDSFKIKH 438 (LPS binding) 6,376, 462

BPI fragment 2 SSOISMVPNVGLKFSISNANIKISGKWKAOKRFLK 439 (LPS binding) 6,376, 462 US 2010/0316643 A1 Dec. 16, 2010 34

TABLE 4 - continued Additional illustrative targeting moieties. Targeting Moiety/ SEQ ID Organism Structure/sequence NO BPI fragment 3 WHVHISKSKVGWLIOLFHKKIESALRNK 44 O (LPS binding) 6,376, 462 LBP fragment 1 AAQEGLLALOSELLRITLPDFTGDLRIPH 441 (LPS binding) 6,376, 462 LBP fragment 2 HSALRPVPGOGLSLSISDSSIRVOGRWKVRKSFFK 442 (LPS binding) 6,376, 462 LBP fragment 3 WEVDMSGDLGWLLNLFHNOIESKFOKV 443 (LPS binding) 6,376, 462 B. anthracis spore ATYPLPIR 444 binding (WO/1999/O36 O81) Bacilius spore binding peptides of 5-12 amino acids containing the sequence 445 (WO/1999/O36 O81) Asn-His-Phe-Leu. peptides of 5-12 amino acids containing the sequence 446 Asn-His-Phe-Leu-Pro Thr-Ser-Glu-Asn-Val-Arg-Thr (TSQNVRT) 447 A peptide of formula Thr-Tyr-Pro-X-Pro-X-Arg 4 48 (TYPXPXR) where X is a Ile, Wall or Lieu. A peptide having the sequence TSQNVRT. 449 A peptide having the sequence TYPLPIR 450 LPS binding peptide 1 TFRRLKWK 451 (6,384, 188) LPS BP 2 (6,384, 188) RWKVRKSFFKLO 452 LPS BP 3 (6,384, 188) KWKAOKRFLKMS 453 Pseudomonas pilin KCTSDODEOFIPKGCSK 454 binding peptide (5, 494, 672) Patents and patent publications disclosing the referenced antibodies are identified in the table.

0089. In certain embodiments the targeting moieties can antibody itself can provide anti-microbial activity in addition comprise other entities, particularly when utilized with an to the activity provided by effector moiety since the antibody antimicrobial peptide as described, for example, in Table 2. may engage an immune system effector (e.g., a T-cell) and Illustrative targeting moieties can include a polypeptide, a thereby elicit an antibody-associated immune response, e.g., a humoral immune response. peptide, a small molecule, a ligand, a receptor, an antibody, a 0092 Antibodies that bind particular target microorgan protein, or portions thereof that specifically interact with a isms can be made using any methods readily available to one target microbial organism, e.g., the cell Surface appendages skilled in the art. For example, as described in U.S. Pat. No. Such as flagella and pili, and Surface exposed proteins, lipids 6,231.857 (incorporated herein by reference) three mono and polysaccharides of a target microbial organism. clonal antibodies, i.e., SWLA1, SWLA2, and SWLA3 have 0090 Targeting Antibodies. been made against S. mutans. Monoclonal antibodies 0091. In certain embodiments the targeting moieties can obtained from non-human animals to be used in a targeting comprise one or more antibodies that bind specifically or moiety can also be humanized by any means available in the preferentially a microorganism or group of microorganisms art to decrease their immunogenicity and increase their ability (e.g., bacteria, fungi, yeasts, protozoa, Viruses, algae, etc.). to elicit anti-microbial immune response of a human. Illus The antibodies are selected to bind an epitope characteristic trative microorganisms and/or targets to which antibodies or the particular target microorganism(s). In various embodi may be directed are shown, for example, in Tables 5. ments such epitopes orantigens are typically is gram-positive 0093 Various forms of antibody include, without limita or gram-negative specific, or genus-specific, or species-spe tion, whole antibodies, antibody fragments (e.g., (Fab'), cific, or strain specific and located on the Surface of a target Fab', etc.), single chain antibodies (e.g., ScPV), minibodies, microbial organism. The antibody that binds the epitope or Di-miniantibody, Tetra-miniantibody, (sclv), Diabody, antigen can direct an anti-microbial peptide moiety or other scDiabody, Triabody, Tetrabody, Tandem diabody, VHH, effector to the site. Furthermore, in certain embodiments the nanobodies, affibodies, unibodies, and the like. US 2010/0316643 A1 Dec. 16, 2010

0094 Methods of making such antibodies are well known also well known to those of skill in the art. The Camelidae to those of skill in the art. In various embodiments, such heavy chain antibodies are found as homodimers of a single methods typically involve providing the microorganism, or a heavy chain, dimerized via their constant regions. The vari component thereof for use as an antigen to raise an immune able domains of these camelidae heavy chain antibodies are response in an organism or for use in a screening protocol referred to as V. domains or V, and can be either used per (e.g., phage or yeast display). se as nanobodies and/or as a starting point for obtaining 0095 For example, polyclonal antibodies are typically nanobodies. Isolated V retain the ability to bind antigen raised by one or more injections (e.g. Subcutaneous or intra with high specificity (see, e.g., Hamers-Casterman et al. muscular injections) of the target microorganism(s) or com (1993) Nature 363: 446-448). In certain embodiments such ponents thereof into a suitable non-human mammal (e.g., V. domains, or nucleotide sequences encoding them, can be mouse, rabbit, rat, etc.). derived from antibodies raised in Camelidae species, for 0096. If desired, the immunizing microorganism or anti example in camel, dromedary, llama, alpaca and guanaco. gen derived therefrom can be administered with or coupled to Other species besides Camelidae (e.g. shark, pufferfish) can a carrier protein by conjugation using techniques that are produce functional antigen-binding heavy chain antibodies, well-known in the art. Such commonly used carriers which from which (nucleotide sequences encoding) Such naturally are chemically coupled to the peptide include keyhole limpet occurring V can be obtained, e.g. using the methods hemocyanin (KLH), thyroglobulin, bovine serum albumin described in U.S. Patent Publication US 2006/0211088. (BSA), and tetanus toxoid. The coupled peptide is then used 0103) In various embodiments, for use in therapy, human to immunize the animal (e.g. a mouse or a rabbit). proteins are preferred, primarily because they are not as likely 0097. The antibodies are then obtained from blood to provoke an immune response when administered to a samples taken from the mammal. The techniques used to patient. Comparisons of camelid V, with the V. domains of develop polyclonal antibodies are known in the art (see, e.g., human antibodies reveals several key differences in the Methods of Enzymology, “Production of Antisera With Small framework regions of the camelid V. domain correspond Doses of Immunogen: Multiple Intradermal Injections'. ing to the V/V, interface of the human V. domains. Muta Langone, etal. eds. (Acad. Press, 1981)). Polyclonal antibod tion of these human residues to V resembling residues has ies produced by the animals can be further purified, for been performed to produce "camelized human V. domains example, by binding to and elution from a matrix to which the that retain antigenbinding activity, yet have improved expres peptide to which the antibodies were raised is bound. Those of sion and solubility. skill in the art will know of various techniques common in the 0104 Libraries of single V domains have also been immunology arts for purification and/or concentration of derived for example from V genes amplified from genomic polyclonal antibodies, as well as monoclonal antibodies see, DNA or from mRNA from the spleens of immunized mice for example, Coligan, et al. (1991) Unit 9, Current Protocols and expressed in E. coli (Ward et al. (1989) Nature 341: in Immunology, Wiley InterScience). 544-546) and similar approaches can be performed using the 0098. In certain embodiments the antibodies produced V domains and/or the V, domains described herein. The will be monoclonal antibodies (“mabs'). The general isolated single VH domains are called “dAbs' or domain method used for production of hybridomas secreting mAbs is antibodies. A “dAb’ is an antibody single variable domain well known (Kohler and Milstein (1975) Nature, 256:495 (V or V.) polypeptide that specifically binds antigen. A 0099 Antibody fragments, e.g. single chain antibodies “dAb' binds antigen independently of other V domains; how (ScPV or others), can also be produced/selected using phage ever, as the term is used herein, a “dAb’ can be present in a display and/or yeast display technology. The ability to homo- or heteromultimer with other V, or V, domains where express antibody fragments on the Surface of viruses that the other domains are not required for antigen binding by the infect bacteria (bacteriophage or phage) or yeasts makes it dAb, i.e., where the dAb binds antigen independently of the possible to isolate a single binding antibody fragment, e.g., additional V, or V, domains. from a library of greater than 10" nonbinding clones. To 0105. As described in U.S. Patent Publication US 2006/ express antibody fragments on the Surface of phage (phage 0211088 methods are known for the cloning and direct display) or yeast, an antibody fragment gene is inserted into screening of immunoglobulin sequences (including but not the gene encoding a phage surface protein (e.g., pIII) and the limited to multivalent polypeptides comprising: two or more antibody fragment-pII fusion protein is displayed on the variable domains—or antigen binding domains—and in par phage surface (McCafferty et al. (1990) Nature, 348: 552 ticular V. domains or V. domains; fragments of V, V, or 554; Hoogenboom et al. (1991) Nucleic Acids Res. 19:4133 V. domains, such as CDR regions, for example CDR3 4137). regions; antigen-binding fragments of conventional 4-chain 0100 Since the antibody fragments on the surface of the antibodies such as Fab fragments and ScFv's, heavy chain phage or yeast are functional, phage bearing antigen binding antibodies and domain antibodies; and in particular of V. antibody fragments can be separated from non-binding phage sequences, and more in particular of V, Sequences) that can by antigen affinity chromatography (McCafferty et al. (1990) be used as part of and/or to construct such nanobodies. Nature, 348: 552-554). Depending on the affinity of the anti 0106 Methods and procedures for the production of VHH/ body fragment, enrichment factors of 20 fold-1,000,000 fold nanobodies can also be found for example in WO94/04678, are obtained for a single round of affinity selection. WO 96/34103, WO 97/49805, WO 97/498.05 WO 94/25591, 0101 Human antibodies can be produced without prior WO 00/43507 WO 01/90190, WO 03/025020, WO immunization by displaying very large and diverse V-gene 04/062551, WO 04/041863, WO 04/041865, WO 04/041862, repertoires on phage (Marks et al. (1991).J. Mol. Biol. 222: WO 04/041867, PCT/BE2004/000159, Hamers-Casterman 581-597. et al. (1993) Nature 363: 446: Riechmann and Muyldermans 0102. In certain embodiments, nanobodies can be used as (1999).J. Immunological Meth., 231: 25-38; Vu et al. (1997) targeting moieties. Methods of making VH (nanobodies) are Molecular Immunology, 34(16-17): 1121-1131; Nguyenetal. US 2010/0316643 A1 Dec. 16, 2010 36

(2000) EMBO.J., 19(5): 921-930; Arbabi Ghahroudi et al. 0111. In addition, antibodies (targeting moieties) that bind (19997) FEBS Letters 414: 521-526; van der Linden et al. other microorganisms can readily be produced using, for (2000).J. Immunological Meth., 240: 185-195; Muyldermans example, the methods described above. (2001) Rev. Molecular Biotechnology 74: 277-302; Nguyen (O112 Porphyrins. etal. (2001) Adv. Immunol. 79: 261, and the like, which are all 0113. In certain embodiments porphyrins, or other photo incorporated herein by reference. sensitizing agents, can be used as targeting moieties in the 0107. In certain embodiments the antibody targeting moi constructs described herein. In particular, metalloporphyrins, ety is a unibody. Unibodies provide an antibody technology particularly a number of non-iron metalloporphyrins mimic that produces a stable, Smaller antibody format with an antici heme in their molecular structure and are actively accumu pated longer therapeutic window than certain Small antibody lated by bacteria via high affinity heme-uptake systems. The formats. In certain embodiments unibodies are produced same uptake systems can be used to deliver antibiotic-por from IgG4 antibodies by eliminating the hinge region of the phyrin and antibacterial-porphyrin conjugates. Illustrative antibody. Unlike the full size IgG4 antibody, the half mol targeting porphyrins Suitable for this purpose are described in ecule fragment is very stable and is termed a uniBody. Halv U.S. Pat. No. 6,066,628 and shown herein, for example, in ing the IgG4 molecule left only one area on the UniBody that FIGS. 1 and 2. can bind to a target. Methods of producing unibodies are 0114 For example, certain artificial (non-iron) metal described in detail in PCT Publication WO2007/059782, loporphyrins (MPs) (Ga-IX, Mn-IX.) are active against which is incorporated herein by reference in its entirety (see, Gram-negative and Gram-positive bacteria and acid-fast also, Kolfschoten et al. (2007) Science 317: 1554-1557). bacilli (e.g., Y. enterocolitica, N. meningitides, S. marcescens, 0108 Affibody molecules are class of affinity proteins E. coli, P. mirabills, K. pneumoniae, K. Oxytoca, Ps. aerugi based on a 58-amino acid residue protein domain, derived from one of the IgG-binding domains of staphylococcal pro nosa, C. freundii, E. aerogenes, F. menigo septicum, S. aureus, tein A. This three helix bundle domain has been used as a B. subtilis, S. pyogenes A, E. faecalis, M. Smegmatis, M. bovis, scaffold for the construction of combinatorial phagemid M. tuber, S. cerevisiae) as described in Tables 1-5 of U.S. Pat. libraries, from which Affibody variants that target the desired No. 6,066,628. These MPs can be used as targeting moieties molecules can be selected using phage display technology against these microorganisms. (see, e.g., Nord et al. (1997) Nat. Biotechnol. 15: 772-777: 0115 Similarly, some MPs are also growth-inhibitory Ronmark et al. (2002) Eur: J. Biochem., 269: 2647-2655). against yeasts, indicating their usefulness targeting moieties Details of Affibodies and methods of production are known to to target Candida species (e.g., Candida albicans, C. krusei, those of skill (see, e.g., U.S. Pat. No. 5,831,012 which is C. pillosus, C. glabrata, etc.) and other mycoses including but incorporated herein by reference in its entirety). not limited to those caused by as Trichophyton, Epidermo 0109. It will also be recognized that antibodies can be phyton, Histoplasma, Aspergillus, Cryptococcus, and the prepared by any of a number of commercial services (e.g., like. Berkeley antibody laboratories, Bethyl Laboratories, Anawa, 0116 Porphyrins, and other photosensitizers, also have Eurogenetec, etc.). antimicrobial activity. Accordingly, in certain embodiments, 0110 Illustrative antibodies that bind various microorgan the porphyrins, or other photosensitizers, can be used as isms are shown in Table 5. effectors (e.g., attached to targeting peptides as described herein). In various embodiments the porphyrins or other pho TABLE 5 tosensitizers can provide a dual functionality, e.g., as a tar geting moiety and an antimicrobial and can be attached to a Illustrative antibodies that bind target microorganisms. targeting peptide and/or to an antimicrobial peptide as described herein. Source Antibody 0117 Illustrative porphyrins and other photosensitizers 7,195,763 Polyclonal/monoclonal binds specific Gram(+) are shown in FIGS. 1-11 and described in more detail in the cell wall repeats 6,939,543 Antibodies against G(+) LTA discussion of effectors below. 7,169,903 Antibodies against G(+) peptidoglycan 0118 Pheromones. 6,231,857 Antibody against S. militans (Shi) 5,484,591 Gram(-) binding antibodies 0119. In certain embodiments, pheromones from micro US 2007/0231321 Diabody binding to Streptococcus surface organisms can be used as targeting moieties. Illustrative antigen III pheromones from bacteria and fungi are shown in Table 6. In US 2003,O124635 Antibody against S. militans certain embodiments, chimeric moieties are contemplated US 2006.O1273.72 Antibodies to Actinomyces naeslundii, Lactobacilius casei comprising a targeting moiety comprising or consisting of the US 2003,OO92O86 Antibody to S. sobrinus amino acid sequence (or retro or retro-inverso or beta) sequence of a peptide shown in Table 6 attached to one or more of the peptides shown in Table 2.

TABLE 6 Illustrative bacterial and fungal pheromones utilizable as targeting moieties.

Bacterial Pheromones Locus tag Product Sequence SEO ID iPD1 Enterococcus MKOOKKHIAALLF 45.5 faecallis ALILTLWS US 2010/0316643 A1 Dec. 16, 2010 37

TABLE 6-continued Illustrative bacterial and fungal pheromones utilizable as targeting moieties. Bacterial Pheromones Locus tag Product Sequence SEQ ID gi 113947 Igb|AAB35253.1| iAM373 sex pheromone SIFTLWA 456 inhibito Enterococcus faecallis, Peptide, 7 aa gi 15412 sp|P13268. 1|CAD1 ENTFA Sex pheromone CAD1 LFSLWLAG 457 gi Sex pheromone cAM373 AIFILAS 458 (Clumping-inducing agent) (CIA) gi 1724 Olsp|P13269.1|CPD1 ENTFA Sex pheromone cPD1 FLWMFLSG 459 gi 2056953 Igb|AAG48144.1|AF322594 1 putative peptide DSIRDWSPTFNKIRR 460 pheromone ProA WFDGLFK Lactobacilius paracasei gi Sex pheromone inhibitor MSKRAMKKIIPLIT 461 determinant precursor LFWWTLVG (i.AD1) gi 263 62994 emb|CAM35812.1 precursor of pheromone KDEIYWKPS 462 peptide ComX Bacillus amyloliquefaciens FZE42 gi pheromone YSTCDFIM 463 gi 59004 42 refNP 345046.1 peptide pheromone BlpC GLWEDLLYNINRY 464 Streptococcus AHYIT pneumoniae TIGR4 gi 617436emb|CAA66791.1 competence pheromone DIRHRINNSIWRDIF 465 Streptococcus gordonii LKRK gi 61744 Olemb|CAA66786.1 competence pheromone DWRSNKIRLWWEN 466 Streptococcus gordonii IFFNKK gi ComX pheromone PTTRENDG 467 precursor Bacilius mojavensis gi ComX pheromone LOIYTNGNWWPS 468 precursor Bacilius mojavensis gi 293778O8|refNP 816936.1 sex pheromone inhibitor MSKRAMKKIIPLIT 469 determinant Enterococcus LFWWTLVG faecalis V583 gi 3342125.gb|AAC27522. 1| putative pheromone GAGKNLIYGMGYG 47 O Enterococcus faecium YLRSCNRL gi 41O18893 Competence-stimulating EMRLSKFFRDFILO 471 peptide type 1 precursor (CSP-1) gi 5.7489126 PcfP Enterococcus WSEIEINTKOSN 472 faecallis gi 5.7489.152 Prg T Enterococcus HISKERFEAY 473 faecallis gi 58616083 ref|P 1957 61.1 UvaF Enterococcus 474 faecallis RKDHRTAR gi 5861. 6111 reflyP 1958O2.1 PcfP Enterococcus WSEIEINTKOSN faecallis gi 5861. 6132 ref|P 1957 69.1 ProgQ Enterococcus MKTTLKKLSRYIA 476 faecallis WWIAITLIFI US 2010/0316643 A1 Dec. 16, 2010 38

TABLE 6- continued Illustrative bacterial and fungal pheromones utilizable as targeting moieties. Bacterial Pheromones Locus tag Product Sequence SEQ ID gi 58616137|ref|P 195772.1 Prg T Enterococcus HISKERFEAY 477 faecallis gi Competence-stimu ating 478 peptide precursor (CSP) RTK gi Competence-stimu ating EMRKPDGALFNLF 479 peptide precursor (CSP) RRR gi Competence-stimu ating EMRKSNNNFFHFL peptide precursor (CSP) RRI gi Competence-stimu ating ESRLPKIRFDFIFPR 481 peptide precursor (CSP) gi Competence-stimu ating EIROTHNIFFNFFKRR 482 peptide precursor (CSP) gi Competence-stimu ating DWRISETIRNLIFPR 483 peptide precursor (CSP) RK gi cCB1bacterial sex WAWLWLGA 484 pheromone Enterococcus faecallis, Peptide, 8 aa gi ComX pheromone FFEDDKRKSFI 485 precursor Bacilius subtilis gi ComX pheromone FFEDDKRKSFI 486 precursor Bacilius subtilis gi 2827 2731 emb|CAD656.60.1 accessory gene regulator MKOKMYEAIAHL 487 protein D, peptide KYVGAKOLVMCC pheromone precursor WGIWFETKIPDE RK Lactobacilius plantarum WCFS1) gi|283.7989 o|ref INP 786782. 1| accessory gene regulator MKOKMYEAIAHL 488 protein D, peptide KYVGAKOLVMCC pheromone precursor WGIWFETKIPDE RK Lactobacilius plantarum WCFS1 gi 5.74891. OS Prg F Enterococcus VVAYVITOVGAI RF 489 faecallis gi 58616090 ref|P 195779.1 Prg F Enterococcus VVAYVITOVGAI RF 490 faecallis gi 58 616 38 ref|P 1957 62.1 PrgN Enterococcus LLKLODDYLLHLE 491 faecallis RHRRTKKIIDEN gi 5.74891.17 Pcf F Enterococcus EDIKDLTDKVOSLN 492 faecallis ALWOSELNKLIKRK D gi 5.74891.19 PcfH Enterococcus WFLDFSDWLSKWP 493 faecallis SKLWAE gi 5861 6102 ref|P 195792.1 Pcf F Enterococcus EDIKDLTDKVOSLN 494 faecallis ALWOSELNKLIKRK gi 5861 6104 ref|YP 195794.1 Pof Enterococcus WFLDFSDWLSKWP 495 faecallis SKLWAE

US 2010/0316643 A1 Dec. 16, 2010

TABLE 6-continued Illustrative bacterial and fungal pheromones utilizable as targeting moieties. Bacterial Pheromones Locus tag Product Sequence SEQ ID gi|3025.095 sp|Q07549. 11SNA4 YEAST Protein SNA4 ARNVYPSVETPLLO 53 O GAAPHDNKQSLVE SPPPYVP

RecName: Full = Protein FLKKLNRKIASIFN 531 ZEO1; AltName: Full = Zeocin resistance protein 1

RecName: Full Protein DSISROGSISSGPPP 532 IGO2 RSPNK

0120 Effectors. enclosed in a silica shell can be easily derivatized for coupling 0121 Any of a wide number of effectors can be coupled to to a biological molecule (Bruchez et al. (1998) Science, 281: targeting moieties as described herein to preferentially 2013-2016). Similarly, highly fluorescent quantum dots (zinc deliver the effector to a target organism and/or tissue. Illus Sulfide-capped cadmium selenide) have been covalently trative effectors include, but are not limited to detectable coupled to biomolecules for use in ultrasensitive biological labels, Small molecule antibiotics, antimicrobial peptides, detection (Warren and Nie (1998) Science, 281: 2016-2018). porphyrins or other photosensitizers, epitope tags/antibodies 0.126 Invarious embodiments spin labels are provided by for use in a pretargeting protocol, microparticles and/or reporter molecules with an unpaired electron spin which can microcapsules, nanoparticles and/or nanocapsules, "carrier' be detected by electron spin resonance (ESR) spectroscopy. vehicles including, but not limited to lipids, liposomes, den Illustrative spin labels include organic free radicals, transi drimers, cholic acid-based peptide mimics or other peptide tional metal complexes, particularly Vanadium, copper, iron, mimics, steroid antibiotics, and the like. and manganese, and the like. Exemplary spin labels include, 0.122 Detectable Labels. 0123. In certain embodiments chimeric moieties are pro for example, nitroxide free radicals. vided comprising a targeting moiety (e.g. as described in I0127. Means of detecting such labels are well known to Table 2) attached directly or through a linker to a detectable those of skill in the art. Thus, for example, where the label is label. Such chimeric moieties are effective for detecting the a radioactive label, means for detection include a scintillation presence and/or quantity, and/or location of the microorgan counter or photographic film as in autoradiography. Where ism(s) to which the targeting moiety is directed. Similarly the label is a fluorescent label, it may be detected by exciting these chimeric moieties are useful to identify cells and/or the fluorochrome with the appropriate wavelength of light tissues and/or food stuffs and/or other compositions that are and detecting the resulting fluorescence, e.g., by microscopy, infected with the targeted microorganism(s). visual inspection, via photographic film, by the use of elec 0124 Detectable labels suitable for use in such chimeric tronic detectors such as charge coupled devices (CCDS) or moieties include any composition detectable by spectro photomultipliers and the like. Similarly, enzymatic labels scopic, photochemical, biochemical, immunochemical, elec may be detected by providing appropriate Substrates for the trical, optical, or chemical means. Illustrative useful labels enzyme and detecting the resulting reaction product. Finally, include, but are not limited to, biotin for staining with labeled simple colorimetric labels may be detected simply by observ streptavidin conjugates, avidin or streptavidin for labeling ing the color associated with the label. with biotin conjugates fluorescent dyes (e.g., fluorescein, texas red, rhodamine, green fluorescent protein, and the like, 0128. Antibiotics. see, e.g., Molecular Probes, Eugene, Oreg., USA), radiola I0129. In certain embodiments chimeric moieties are pro bels (e.g., H, 125I, ss, 1-C, 32P 99Tc, 20Pb, 67Ga Ga, vided comprising a targeting moiety (e.g. as described in 7As, In, 113In, 7Ru, 62Cu, 641Cu, 52Fe, 52"Mn, scr, Table 2) attached directly or through a linker to a small 186Re 188Re 77As 90Y. 67Cu 169Er 12|Sn 127Te 142Pr molecule antibiotic and/or to a carrier (e.g., a lipid or lipo 143Pr s 198A. 199A 16i Tb 69Pd 65Dy 49Pm 5Pm. Some, a polymer, etc.) comprising a small molecule antibiotic 153sm, 157Gd, 159Gd, 166Ho, 172Tm, 1655, 1771, 105Rh (e.g., an antibiotics shown in Table 7). '''Ag, and the like), enzymes (e.g., horse radish peroxidase, alkaline phosphatase and others commonly used in an TABLE 7 ELISA), various colorimetric labels, magnetic or paramag netic labels (e.g., magnetic and/or paramagnetic nanopar Illustrative antibiotics for use in the ticles), spin labels, radio-opaque labels, and the like. Patents chimeric moieties described herein. teaching the use of such labels include, for example, U.S. Pat. Class Generic Name Brand Name Nos. 3,817,837; 3,850,752; 3,939,350; 3,996.345; 4,277,437; Aminoglycosides Amikacin Amikin 4,275,149; and 4,366,241. Gentamicin Garamycin 0.125. It will be recognized that fluorescent labels are not Kanamycin Kantrex to be limited to single species organic molecules, but include Neomycin inorganic molecules, multi-molecular mixtures of organic Netilmicin Netromycin and/or inorganic molecules, crystals, heteropolymers, and the Streptomycin like. Thus, for example, CdSe CdS core-shell nanocrystals US 2010/0316643 A1 Dec. 16, 2010 42

TABLE 7-continued TABLE 7-continued

Illustrative antibiotics for use in the Illustrative antibiotics for use in the chimeric moieties described herein. chimeric moieties described herein.

Class Generic Name Brand Name Class Generic Name Brand Name Tobramycin Nebcin Tetracyclines Demeclocycline Paromomycin Humatin Doxycycline Vibramycin Carbacephem Loracarbef Lorabid Minocycline Minocin Carbapenems Ertapenem Invanz Oxytetracycline Terracin Doripenem Finibax Tetracycline Sumycin Imipenem Cilastatin Primaxin Cationic steroid squalamine Meropenem Merrem antibiotics CSA-8 Cephalosporins Cefadroxi Duricef CSA-11 (First Cefazolin Ancef CSA-13 generation) Cefalotin or Cefalothin Keflin CSA-15 Cefalexin Keflex CSA-25 Cephalosporins Cefaclor Ceclor CSA-46 (Second Cefamandole Mandole CSA-54 generation) Cefoxitin Mefoxin CSA-90 Cefprozil Cefail CSA-97 Cefuroxime Ceftin, Zinnat Others Arsphenamine Salvarsan Cephalosporins Cefixime Suprax Chloramphenicol Chloromycetin (Third Cefinir Omnicef Clindamycin Cleocin generation) Cefitoren Spectracef Lincomycin CefoperaZone Cefobid Ethambutol Cefotaxime Claforan Fosfomycin Cefpodoxime Fusicic acid Fucidin Ceftazidime Fortaz Furazolidone Ceftibuten Cedax Isoniazid Ceftizoxime Linezolid Zyvox Ceftriaxone Rocephin Metronidazole Flagyl Cephalosporins Cefepime Maxipime Mupirocin Bactroban (Fourth Nitrofurantoin Macrodantin, generation) Macrobid Cephalosporins Ceftobiprole Platensinycin (Fifth Pyrazinamide generation) Quinupristin/Dalfopristin Syncercid Glycopeptides Teicoplanin Rifampin or Rifampicin Vancomycin Vancocin Tinidazole Macrollides Azithromycin Zithromax Clarithromycin Biaxin Dirithromycin 0.130 Porphyrins and Non-Porphyrin Photosensitizers. Erythromycin Erythocin, I0131. In certain embodiments, porphyrins and other pho Erythroped Roxithromycin tosensitizers can be used as targeting moieties and/or as effec Troleandomycin tors in the methods and compositions of this invention. A Telithromycin Ketek photosensitizer is a drug or other chemical that increases Monobactams Aztreonam photosensitivity of the organism (e.g., bacterium, yeast, fun Penicillins Amoxicillin Novamox, Amoxil gus, etc.). As targeting moieties the photosensitizers (e.g., Ampicillin porphyrins) are preferentially uptaken by the target microor Azlocillin Carbenicillin ganisms and thereby facilitate delivery of the chimeric moiety Cloxacillin to the target microorganism. Dicloxacillin 0.132. As effectors, photosensitizers can be useful in pho Flucloxacillin Floxapen todynamic antimicrobial chemotherapy (PACT). In various Mezlocillin embodiments PACT utilizes photosensitizers and light (e.g., Meticillin Nafcillin visible, ultraviolet, infrared, etc.) in order to give a phototoxic Oxacillin response in the target organism(s), often via oxidative dam Penicillin age. Piperacillin 0.133 Currently, the major use of PACT is in the disinfec Ticarcillin tion of blood products, particularly for viral inactivation, Polypeptides Bacitracin although more clinically-based protocols are used, e.g. in the Colistin Polymyxin B treatment of oral infection or topical infection. The technique Quinolones Mafenide has been shown to be effective in vitro against bacteria (in Prontosil (archaic) cluding drug-resistant strains), yeasts, viruses, parasites, and Sulfacetamide the like. Sulfamethizole 0.134 Attaching a targeting moiety (e.g., a targeting pep Sulfanilimide (archaic) tide as shown in Table 2) to the photosensitizer, e.g., as SulfaSalazine Sulfisoxazole described herein, provides a means of specifically or prefer Trimethoprim Trimethoprim Bactrim entially targeting the photosensitizer(s) to particular species Sulfamethoxazole or strains(s) of microorganism. (Cotrimoxazole) (TMP-SMX) 0.135 A wide range of photosensitizers, both natural and synthetic are known to those of skill in the art (see, e.g., US 2010/0316643 A1 Dec. 16, 2010

Wainwright (1998).J. Antimicrob. Chemotherap. 42: 13-28). 0142. In typical photodynamic antimicrobial chemo Photosensitizers are available with differing physicochemi therapy (PACT) the targeted photosensitizer is “activated by cal make-up and light-absorption properties. In various the application of a light Source (e.g., a visible light source, an embodiments photosensitizers are usually aromatic mol ultraviolet light source, an infrared light source, etc.). PACT ecules that are efficient in the formation of long-lived triplet applications however need not be limited to topical use. excited states. In terms of the energy absorbed by the aro Regions of the mouth, throat, nose, sinuses are readily illu matic-system, this again depends on the molecular structure minated. Similarly regions of the gut can readily be illumi involved. For example: furocoumarin photosensitizers (pso nated using endoscopic techniques. Other internal regions ralens) absorb relatively high energy ultraviolet (UV) light (c. can be illumined using laparoscopic methods or during other 300-350 nm), whereas macrocyclic, heteroaromatic mol Surgical procedures. For example, in certain embodiments ecules Such as the phthalocyanines absorb lower energy, near involving the insertion or repair or replacement of an implant infrared light. able device (e.g., a prosthetic device) it contemplated that the 0.136 Illustrative photosensitizers include, but are not lim device can be coated or otherwise contacted with a chimeric ited to porphyrinic macrocyles (especially porphyrins, chlo moiety comprising a targeting moiety attached to a photosen rines, etc., see, e.g., FIGS. 1 and 2). In particular, metallopor sitizer as described herein. During the Surgical procedure phyrins, particularly a number of non-iron metalloporphyrins and/or just before closing, the device can be illuminated with mimic heme in their molecular structure and are actively an appropriate light source to activate the photosensitizer. accumulated by bacteria via high affinity heme-uptake sys 0143. The targeted photosensitizers and uses thereof tems. The same uptake systems can be used to deliver antibi described herein are illustrative and not to be limiting. Using otic-porphyrin and antibacterial-porphyrin conjugates. Illus the teachings provided herein, other targeted photosensitizers trative targeting porphyrins Suitable for this purpose are and uses thereof will be available to one of skill in the art. described in U.S. Pat. No. 6,066,628 and shown herein in 0144 Antimicrobial Peptides. FIGS. 1 and 2. (0145. In certain embodiments the chimeric moieties 0.137 For example, certain artificial (non-iron) metal described herein include one or more antimicrobial peptides loporphyrins (MPs) (Ga-IX, Mn-IX.) are active against (e.g., certain peptides shown in Table 2 and/or Table 10) as Gram-negative and Gram-positive bacteria and acid-fast effectors. Thus, for example, in certain embodiments, where bacilli (e.g., Y. enterocolitica, N. meningitides, S. marcescens, the peptides described in Table 2 are exploited for their tar E. coli, P. mirabilis, K. pneumoniae, K. Oxytoca, Ps, aerugi geting ability, chimeric moieties are contemplated compris nosa, C. freundii, E. aerogenes, F. menigosepticum, S. aureus, ing one or more of the targeting peptides of Table 2 attached B. subtilis, S. pyogenes A, E. faecalis, M. Smegmatis, M. bovis, to one or more of the antimicrobial peptides of Table 10. In M. tuber, S. cerevisiae) as described in Tables 1-5 of U.S. Pat. certain embodiments chimeric moieties are contemplated No. 6,066,628. These MPs can be used as targeting moieties comprising one or more of the targeting peptides of Table 2 against these microorganisms. attached to one or more of the antimicrobial peptides of Table 0138 Similarly, some MPs are also growth-inhibitory 2. In certain embodiments chimeric moieties are contem against yeasts, indicating their usefulness targeting moieties plated comprising other targeting moieties (e.g., porphyrins, to target Candida species (e.g., Candida albicans, C. krusei, antibodies, etc.) attached to one or more of the antimicrobial C. pillosus, C. glabrata, etc.) and other mycoses including but peptides of Table 2. not limited to those caused by as Trichophyton, Epidermo 014.6 Antimicrobial peptides (also called host defense phyton, Histoplasma, Aspergillus, Cryptococcus, and the peptides) are an evolutionarily conserved component of the like. innate immune response and are found among all classes of 0.139. Other photosensitizers include, but are not limited to life. Unmodified, these peptides are potent, broad spectrum cyanines (see, e.g., FIG. 6) and phthalocyanines (see, e.g., antibiotics which demonstrate potential as novel therapeutic FIG. 4), azines (see, e.g., FIG. 5) including especially meth agents. Antimicrobial peptides have been demonstrated to kill ylene blue and toluidine blue, hypericin (see, e.g., FIG. 8), Gram-negative and Gram-positive bacteria (including strains acridines (see, e.g., FIG.9) including especially Rose Bengal that are resistant to conventional antibiotics), mycobacteria (see, e.g., FIG. 10), crown ethers (see, e.g., FIG. 11), and the (including Mycobacterium tuberculosis), enveloped viruses, like. and fungi. 0140. In certain embodiments the photosensitizers are 0147 Naturally-occurring antimicrobial peptides are typi toxic or growth inhibitors without light activation. For cally short peptides, generally between 12 and 50 amino example, Some non-iron metalloporphyrins (MPs) (see, e.g., acids. These peptides often include two or more positively FIGS. 1 and 2 herein) possess a powerful light-independent charged residues provided by arginine, lysine or, in acidic antimicrobial activity. In addition, haemin, the most well environments, histidine, and frequently a large proportion known natural porphyrin, possesses a significantantibacterial (generally >50%) of hydrophobic residues (see, e.g., Papagi activity that can augmented by the presence of physiological anni et al. (2003) Biotechnol Adv21: 465: Sitaram and Naga concentrations of hydrogen peroxide or a reducing agent. raj(2002) Curr Pharm Des 8: 727; Dürretal. (2006) Biochim. 0141 Typically, when activated by light, the toxicity or Biophys. Acta 1758: 1408-1425). growth inhibition effect is substantially increased. Typically, 0148 Frequently the secondary structures of these mol they generate radical species that affect anything within proX ecules follow 4 themes, including i) C.-helical. ii) B-stranded imity. In certain embodiments to get the best selectivity from due to the presence of 2 or more disulfide bonds, iii) f-hairpin targeted photosensitizers, anti-oxidants can be used to quench or loop due to the presence of a single disulfide bond and/or un-bound photosensitizers, limiting the damage only to cells cyclization of the peptide chain, and iv) extended. Many of where the conjugates have accumulated due to the targeting these peptides are unstructured in free solution, and fold into peptide. The membrane structures of the target cell act as the their final configuration upon partitioning into biological proton donors in this case. membranes. The ability to associate with membranes is a US 2010/0316643 A1 Dec. 16, 2010 44 definitive feature of antimicrobial peptides although mem brane permeabilisation is not necessary. These peptides have TABLE 8- continued a variety of antimicrobial activities ranging from membrane permeabilization to action on a range of cytoplasmic targets. Novel antimicrobial peptides. 014.9 The modes of action by which antimicrobial pep ID Structure/sequence SEQ ID NO tides kill bacteria is varied and includes, but is not limited to disrupting membranes, interfering with metabolism, and tar geting cytoplasmic components. In many cases the exact K-16 FI RK FLQ KLHL 548 mechanism of killing is not known. K-17 FTRKELKFLHL 549 0150. In various embodiments one or more antimicrobial peptides are used alone (e.g., as broad spectrum antimicrobi K- 18 KKFKKFKWLKIL 550 als) and/or are provided as effectors attached to one or more targeting moieties thereby providing a narrower spectrum K-19 LLKLIKLKKLKF 551 (directed) antimicrobial. In certain embodiments one or more antimicrobial peptides are provided as effectors attached to 0152. In certain embodiments peptides that induce alter one or more targeting moieties and/or one or more effectors ations in phenotype or other biological activities can also be thereby providing a component of a multiple effector com used as antimicrobial effector moieties. Illustrative alterna position/strategy. tive peptides are shown in Table 9. 0151. Suitable antimicrobial peptides for this use include, but are not limited to the antimicrobial peptides found in TABLE 9 Table 2, and/or Table 9, and/or Table 10. Novel growth phenotype-inducing or peptides with other activities. TABLE 8 SEQ Novel antimicrobial peptides. ID ID Organism, effect Structure/sequence NO ID Structure/sequence SEQ ID NO G-1 S. mutans: Ca2+ DSSOSDSDSDSNSSNTNSNSSITNG 552 K-1 GLGRVIGRLIKQIIWRR 533 binding

K-2 WYRKRKSILKIYAKLKGWH 534 G-2 S. mutans: biofilm LPGTLHIOAEFPVOLEAGSLIOIFD 553 Structure K-3 AFYORKENVISLDPREWLGFNVTEK 535 G-3 S. mutans : biofilm LACTTPWGAWLYLGAEWCAGAAWI 554 K-4 DKKRWIERIKSFSLRDEWIHFGELCIYWGK 536 Structure YYGAN

K-5 RSSYNGFSKICFLKIEHFGSYSYOGR s37 G-4 S. mutans : EIPIOLANDLANYYDISLDSIFFW 555 Biofilm structure K-6 WLNAISLYGRIG 538 G-5. M. xanthus : RDMTWAGKRPNFLIITTDEE 556 K-7 NYRLWNAIFSKIFKKKFIKF 539 Altered cell morphology K-8 KIL. K. FLF K. KWF 54 O G- 6 M. Xanthus: NTSIWCAWTFAPIKEWPLLWRAGLT 557 K-9 FI RK FLK KW LL 541 Altered cell LRSROS morphology K-10 KLFKFLRKHLL 542 G-7 M. xanthus : OAKVEREVERDLWYTLRRLCDPSG 558 K-11 KIL K FLF K OVF 543 Altered cell SERTK morphology K-12 KIL. K. KLF K FWF 544 G-8 S. mutans : PRMIDIISFHGCHGDHOVWTDPOAT 559 K-13 GIL. K. KLF. T. KWF 5.45 Altered biofilm ALPR Structure K-14 L. R. K. FL H K LF 546

K-15 L. R. KNL R. WLF 47 0153. Other illustrative antimicrobial peptides include, but are not limited to the AMPs of Table 10.

TABL E 1O

Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/AP/main.php).

SEO ID Effector Structure/Sequence No

APOO 274 1BH4, Circulin A GIPCGESCWWIPCISAALGCSCKNKWC 560 (CirA, plant YRN cyclotides, XXC, ZZHp) US 2010/0316643 A1 Dec. 16, 2010 45

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOOO36 1BNB. Beta- defensin. 1 DFASCHTNGGICLPNRCPGHMIOIGICF 561 (cow) RPRWKCCRSW

APOOO47 1BNB, Bovine GPLSCGRNGGVCIPIRCPWPMROIGTC 562 neutrophill beta-defensin FGRPVKCCRSW 12 (BNBD-12, cow) APOO 428 1CO1, MiAMP1 SAFTWWSGPGCNNRAERYSKCGCSAI 563 (Macadamia integrifolia HOKGGYDFSYTGOTAALYNOAGCSG antimicrobial peptide 1, VAHTRFGSSARACNPFGWKSIFIOC plant) APOO154 1CIX, Tachystatin A2 YSRCOLOGFNCVVRSYGLPTIPCCRGL 564 (Horseshoe crabs, TCRSYFPGSTYGRCORY Crustacea, BBS)

APOO145 1CW5, WNYGNGVSCSKTKCSVNWGOAFOER 565 Carnobacteriocin B2 YTAGINSFWSGWASGAGSIGRRP (CnbB2, class IIA bacteriocin, bacteria) APOO153 1CZ6, Androctonin RSVCROIKICRRRGGCYYKCTNRPY 566 (scorpions) APOO152 1D6X, Tritrptic in WRRFPWWWPFLRR 567 (synthetic)

APOO2O1 1D7N, Mastoparan INIKALAALAKKIL 568 (insect) APOO140 1D9J, CecropinA- KWKLFKKIGIGKFLHSAKKF 569 Magainin2 hybrid (synthetic)

APOO178 1DFN, human alpha DCYCRIPACIAGERRYGTCIYOGRLW st O Defensin HNP-3 AFCC (human neutrophil peptide-3, HNP3, human defensin, ZZHh) APO1153 DQC, Tachycitin YLAFRCGRYSPCLDDGPNWNLYSCCS sf1 (horseshoe crabs, FYNCHKCLARLENCPKGLHYNAYLK Crustacea, BBS) WCDWPSKAGCT

APOO 437 DUM, Magainin 2 GIGKYLHSAKKFGKAWWGEIMNS sf2 analog (synthetic)

APOO 451 E4S, Human beta DHYNCVSSGGOCLYSACPIFTKIOGTC sf3 defensin. 1 (HBD-1, YRGKAKCCK human defensin) APOO149 EWS, Rabbit kidney MPCSCKKYCDPWEWIDGSCGLFNSKY sf4 defensin. 1 (RK-1) ICCREK

APOO141 FOE, CecropinA- KWKLFKKIPKFLHSAKKF sts Magainin2 Hybrid (P18, synthetic)

APOO142 FOG, CecropinA- KLKLFKKIGIGKFLHSAKKF 576 Magainin2 Hybrid (synthetic)

APOO143 FOH, CecropinA- KAKLFKKIGIGKFLHSAKKF 577 Magainin2 Hybrid (synthetic)

APOO524 FD4, Human beta GIGDPVTCLKSGAICHPVFCPRRYKOI sf8 defensin 2 (HBD-2, GTCGLPGTKCCKKP human defensin, ZZHh) US 2010/0316643 A1 Dec. 16, 2010 46

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No

APOO438 FJN, Mussel Defensin GFGCPNNYOCHRHCKSIPGRCGGYCG st 9 MGD-1 GWHRLPCTCYRCG

APOO155 FRY, SMAP-29 RGLRRLGRKIAHGWKKYGPTWLRIIRI 58 O (SMAP29, sheep AG cathelicidin)

APOO15 O G89, Indolicidin (cow ILPWKWPWWPWRR 581 cathelicidin, BBN, ZZHa)

APOO156 GR4, Microcin J25. WGIGTPISFYGGGAGHWPEYF 582 inear (MccJ25, bacteriocin, bacteria) APOO151 HR1, Indolicidin P to ILAWKWAWWAWRR 583 A mutant (synthetic)

APOO1.96 HU5, Ovispirin-1 KNLRRIIRKIIHIIKKYG 584 (synthetic)

APOO1.97 HU6, Novispirin G10 KNLRRIIRKGIHIIKKYG 585 (synthetic)

APOO198 HU7, Novispirin T7 KNLRRITRKIIHIIKKYG 586 (synthetic)

APOO445 HVZ, Monkey RTD-1 GFCRCLCRRGVCRCICTR 587 (rhesus theta-defensin-1, minidefensin-1, animal defensin, XXC, BBS, ectin, ZZHa)

APOO 103 i2v, Heliomicin variant DKLIGSCWWGAWNYTSDCNGECLLRG 588 (Hel-LL, synthetic) YKGGHCGSFANWNCWCET

APOO216 ICA Phormia defensin ATCDLLSGTGINHSACAAHCLLRGNR 589 A (insect defensin A) GGYCNGKGWCWCRN

APO1224 Jo3, Gramicidin B WGALAWWWWLFLWLW. 590 (bacteria) APO1225 jo4, Gramicidin C WGALAWWWWLYLWLW. 591 (bacteria)

APOO191 KFP, Gomesin (Gm, ECRRLCYKORCVTYCRGR 592 Spider, XXA)

APOO283 KJ6, Huamn beta GIINTLOKYYCRVRGGRCAVLSCLPKE 593 defensin 3 (HBD-3 EOIGKCSTRGRKCCRRKK human defensin, ZZHh)

APOO 147 KV4, Moricin (insect, AKIPIKAIKTWGKAWGKGLRAINIASTA 594 silk moth) NDWFNFLKPKKRKA

APOO227 L4V, Sapecin (insect, ATCDLLSGTGINHSACAAHCLLRGNR 595 flesh fly) GGYCNGKAWCWCRN

APO1161. L9L, Human GRDYRTCLTIVOKLKKMVDKPTORSV 596 granulysin (hugiran) SNAATRWCTRGRSRWRDWCRNFMRR YQSRVIQGLVAGETAQQICEDLRLCIP STGPL

APOOO26 1LFC, Lactoferricin B FKCRRWOWRMKKLGAPSITCVRRAF 597 (Lfcine, cow, ZZHa)

APOO193 1M4F, human LEAP-1 DTHFPICIFCCGCCHRSKCGMCCKT 598 (Hepcidin 25) US 2010/0316643 A1 Dec. 16, 2010 47

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOO499 MAG Gramicidin. A WGALAWWWWLWLWLW. 5.99 (gA, bacteria)

APOO 403 MMO Termicin ACNFOSCWATCOAOHSIYFRRAF CDR 6OO (termite defensin, insect SOCKCWFWRG defensin)

APOO194 MMC, Ac-AMP2 WGECVRGRCPSGMCCSOFGYCGKGP 6O1 (plant defensin, BBS) KYCGR

APO12O6 MOZ, Mersacidin CTFTLPGGGGVCTLTSECC 6O2 (bacteria) APOO 429 1NKL, Porcine NK- GYFCESCRKIIOKLEDMVGPOPNEDTV 603 Lysin (pig) TOAASQVCDKLKILRGLCKKIMRSFL RRISWDILTGKKPOAICVDIKICKE APOO 633 og 7, Sakacin P/ KYYGNGWHCGKHSCTWDWGTAIGNI 6O4 Sakacin 674 (SakP, GNNAAANWATGGNAGWNK class IIA bacteriocin, bacteria) APOO195 PG1, Protegrin 1 RGGRLCYCRRRFCWCWGR 605 (Protegrin-1, PG-1, pig cathelicidin, XXA, ZZHa, BBBm) APOO928 1PXQ, Subtillosin A NKGCATCSIGAACLWDGPIPDFEIAGA 606 (XXC class I TGLFGLWG bacteriocin, Gram positive bacteria) APOO48 O 1971, Microcin J25 WGIGTPIFSYGGGAGHWPEYF 6O7 (cyclic MccJ25, class I microcins, bacteriocins, Gram-negative bacteria, XXC, BBP) APOO 211 1RKK, Polyphemusin I RRWCFRWCYRGFCYRKCR 608 (crabs, Crustacea) APOO43 O. 1T51, ISCT (Scorpion) ILGKIWEGIKSLF 609 APOO731 1ut3, Spheniscin-2 SFGLCRLRRGFCARGRCRFPSIPIGRCS 610 (Sphe-2, penguin RFVOCCRRVW defensin, avian defensin)

APOOO13 WM5, Aurein 1.2 GLFDIIKKIAESF 611 (frog) APOO214 WO1, Tachyples in I KWCFRWCYRGICYRRCR 61.2 (crabs, Crustacea, XXA, ZZHa)

APOO 644 XCO, Pardaxin 4 GFFALIPKIISSPLFKTLLSAWGSALSSS 613 (Pardaxin P-4, Pardaxin GGOE P4, Pa4, flat fish)

APOO493 XKM Distinctin (two NLVSGLIEARKYLEOLHRKLKNCKW 614 chains for stability and transport? frog)

APOO42O XV3, Penaeidin-4d HSSGYTRPLRKPSRPIFIRPIGCDWCYGI 615 (penaeidin 4, shrimp, PSSTARLCCFRYGDCCHL Crustacea)

APOOO35 YTR Plantaricin. A KSSAYSLOMGATAIKOWKKLFKKWGW 616 (Plina, bacteriocin, bacteria) US 2010/0316643 A1 Dec. 16, 2010 48

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No

APOO16 6 1264, Pleurocidin (fish) GWGSFFKKAAHWGKHWGKAALTHYL 617

APOO780 1Z6W, Human GRRRRSVOWCAVSOPEATKCFOWOR 618 lactoferricin NMRKVRGPPVSCIKRDSPIOCIOA APOO549 12FU, Plectasin (fungi, GFGCNGPWDEDDMOCHNHCKSIKGY 619 fungal defensin) KGGYCAKGGFWCKCY APOO177 12MH, human alpha CYCRIPACIAGERRYGTCIYOGRLWAF 62O Defensin HNP-2 CC (human neutrophil peptide-2, HNP2, human defensin, ZZHh) APOO179 12MM, human alpha WCSCRLWFCRRTELRWGNCLIGGWSFT 621 Defensin HNP-4 YCCTRVD (human neutrophil peptide-4, HNP4, human defensin) APOO180 1ZMP, human alpha OARATCYCRTGRCATRESLSGVCEISG 622 Defensin HD-5 (HD5, RLYRLCCR human defensin) APOO181 12MQ, human alpha STRATCHCRRSCYSTEYSYGTCTVM 623 Defensin HD - 6 (HD6, GINHRFCCL human defensin) APOO399 12RW, Spinigerin HVDKKVADKWLLLKOLRIMRLLTRL 624 (insect, termite) APO1157 12RX, Stomoxyn RGFRKHFNKLWKKWKHTISETAHWAK 625 (insect) DTAWIAGSGAAWWAAT APOO 637 2A2B, Curvac in A/ ARSYGNGVYCNNKKCWVNRGEATOS 626 Sakacin A (CurA, Saka, IIGGMISGWASGLAGM class IIA bacteriocin, bacteria) APOO558 2B68, Co-Def GFGCPGNOLKCNNHCKSISCRAGYCD 627 (Crassostrea gigas AATLWLRCTCTDCNGKK defensin, oyster defensin, animal defensin) APO1154. 2B9K, LCI (bacteria) AIKLVOSPNGNFAASFWLDGTKWIFKS 628 KYYDSSKGYWWGIYEWWDRK

APO1005 2DCV, Tachystatin B1 YWSCLFRGARCRWYSGRSCCFGYYCR 629 (BBS, horseshoe crabs) RDFPGSIFGTCSRRNF APO1006 2DCW, Tachystatin B1 YITCLFRGARCRWYSGRSCCFGYYCR 63 O (BBS, horseshoe crabs) RDFPGSIFGTCSRRNF

APOO275 2ERI, Circulin B (Cir CGESCWFIPCISTLLGCSCKNKWCYRN 631 plant cyclotides, XXC, GWIP ZZHp)

APOO 707 2f3a, LLAA (LL-37- RLFDKIROVIRKF 632 derived aurein 1.2 analog, retro-FK13, synthetic)

APOO 708 2fbs FK-13 (FK13, FKRIVORIKDFLR 633 NMR-discovered LL-37 core peptide, XXA, ZZHs, synthetic)

US 2010/0316643 A1 Dec. 16, 2010 51

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No

APOO187 PO1376, WWCACRRALCLPRERRAGFCRIRGRIH 672 CORTICOSTATIN III PLCCRR (MCP-1, rabbit neutrophill peptide 1, NP-1) (animal defensin, alpha-defensin, rabbit)

APOO188 PO1377, WWCACRRALCLPLERRAGFCRIRGRIH 673 CORTICOSTATIN IV PLCCRR (MCP-2, rabbit neutrophil defensin 2, NP-2, animal defensin, rabbit)

APOOO49 PO1505, Bombinin GIGALSAKGALKGLAKGLAEHFAN 674 (toad) APOO139 PO1507, Cecropin. A KWKLFKKIEKVGONIRDGIIKAGPAVA 675 (insect, ZZHa) WWGOATOIAK APOO128 PO1509, Cecropin B KWKIFKKIEKWGRNIRNGIIKAGPAWA 676 (insect, silk moth) WLGEAKAL APOO131 PO1511, Cecropin D WNPFKELERAGORVRDAIISAGPAVA 677 (insect, moth) TVAQATALAK APOO13 6 PO1518, Crabrolin FLPLILRKIWTAL 678 (insect, XXA) APOO183 PO4142, Cecropin B RWKIFKKIEKMGRNIRDGIWKAGPAIE 6.79 (insect) WLGSAKAI

APOO448 PO42O5, Mastoparan M INIKAIAALAKKLL 68O (MP-M, insect, XXA)

APOO234 PO 6833, SDEKASPDKHHRFSLSRYAKLANRL.A. 681 Seminalplasmin (SPLN, NPKILLETFLSKWIGDRGNRSW calcium transporter inhibitor, caltrin, cow)

APOO314 PO7466, Rabbit WFCTCRGFLCGSGERASGSCTINGWRH 682 neutrophill peptide 5 TLCCRR (NP-5, animal defensin, alpha-defensin)

APOO189 PO7467, Rabbit WSCTCRRFSCGFGERASGSCTWINGWR 683 neutrophill peptide 4 HTLCCRR (NP-4)

APOO186 PO7468, GRCVCRKOLLCSYRERRIGDCKIRGV 684 CORTICOSTATIN II RFPFCCPR (Rabbit neutrophil peptide 3b (NP-3b, rabbit)

APOO185 PO7469, ICACRRRFCPNSERFSGYCRWNGARY 685 CORTICOSTATIN I WRCCSRR (rabbit)

APOO217 PO7469, Rabbit GICACRRRFCPNSERFSGYCRWNGAR 686 neutrophil defensin 3a YVRCCSRR (NP-3a, animal defensin, alpha defensin)

APOOO67 PO7493 Bombolitin II SKITDILAKLGKVLAHW 687 (insect, bee) US 2010/0316643 A1 Dec. 16, 2010 52

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOOO68 PO7494 Bombolitin III IKIMDILAKLGKWLAHW 688 (insect, bee) APOOO69 PO7495, Bombolitin IV INIKDILAKLWKWLGHW 689 (insect, bee)

APOOO7O PO7496, Bombolitin W INWLGILGLIGKALSHL 69 O. (insect, bee) APOO236 PO7504, Pyrularia KSCCRNTWARNCYNWCRLPGTISREIC 691 thionin (Pp-TH, plant) AKKCDCKIISGTTCPSDYPK

APOO23 O PO8375, Sarcotoxin IA GWLKKIGKKIERVGOHTRDATIOGLGI 692 (insect, flesh AQQAANVAATAR APOO231 PO8376, Sarcotoxin IB GWLKKIGKKIERVGOHTRDATIOVIG 693 (insect, flesh WAQQAANVAATAR APOO232 PO8377, Sarcotoxin IC GWLRKIGKKIERVGOHTRDATIOVLGI 694 (insect, flesh AQQAANVAATAR APOOO66 P10521, Bombolitin I IKITTMLAKLGKWLAHW 695 (insect, bee) APOO2O6 P10946, Lantibiotic WKSESLCTPGCVTGALOTCFLOTLTC 696 subtilin (class I NCKISK bacteriocin, bacteria) APOO312 P11477, Cryptdin-2 LRDLWCYCRARGCKGRERMINGTCRK 697 (Crp2, animal defensin, GHLLYMLCCR alpha, mouse) APOO2O5 P13 O68, Nisin. A ITSISLCTPGCKTGALMGCNMIKTATC 698 antibiotic, class I HCSIHWSK bacteriocin, bacteria) APOO 215 P14214, Tachyplesin II RWCFRVCYRGICYRKCR 699 (crabs, Crustacea) APOO212 P1.4216, Polyphemus in RRWCFRWCYKGFCYRKCR 7 OO II (crabs, Crustacea, XXA, ZZHa. Derivatives: T22) APOO134 P14661, Cecropin P1 SWLSKTAKKLENSAKKRISEGIAIAIQ 7 O1 (pig) GGPR

APOOO11 P14662, Bactericidin B2 WNPFKELERAGORVRDAVISAAPAVA 7 O2 (insect) TWGOAAAIARG APOOO32 P14663, Bactericidin B- WNPFKELERAGORVRDAIISAGPAVA 7O3 3 (insect) TWGOAAAIARG

APOOO33 P14664, Bactericidin B- WNPFKELERAGORVRDAIISAAPAVA 704 4 (insect) TWGOAAAIARG

APOOO34 P14665, Bactericidin B- WNPFKELERAGORVRDAVISAAAVAT 7Os 5P (insect) WGOAAAIARG

APOO125 P14666, Cecropin RWKIFKKIEKVGONIRDGIVKAGPAV 706 (insect, silk moth) AWWGOAATI

APOOOO2 P1545 O ABAECIN YVPLPNVPOPGRRPFPTFPGQGPFNPKI 707 (insect, honeybee) KWPOGY

APOO505 P15516, human Histatin DSHAKRHHGYKRKFHEKHHSHRGY 7 OS 5 (ZZHs; derivatives Dh-5) US 2010/0316643 A1 Dec. 16, 2010 53

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOO52O P15516, human Histatin 3 DSHAKRHHGYKRKFHEKHHSHRGYR 7 O9 SNYLYDN

APOO523 P15516, human Histatin 8 KFHEKHHSHRGY 71O APOO226 P17722, Royalisin WTCDLLSFKGOVNDSACAANCLSLGK 711 (insect, honeybee) AGGHCEKWGCICRKTSFKDLWDKRF APOO 213 P18252, Tachyplesin III KWCFRWCYRGICYRKCR 712 (horseshoe crabs, Crustacea) APOO233 P18312, Sarcotoxin ID GWIRDFGKRIERVGOHTRDATIOTIAV 713 (insect, flesh AQQAANWAATLKG APOO2O7 P19578, Lantibiotic TAGPAIRASWKOCOKTLKATRLFTVS 714. PEP5 (class I CKGKNGCK bacteriocin, bacteria)

APOOOO 9 P1966 O. BACTENECIN RFRPPIRRPPIRPPFYPPFRPPIRPPIFPPI 71s 5 (bacs, cow RPPFRPPLGPFP cathelicidin)

APOOO1 O P19661, BACTENECIN RRIRPRPPRLPRPRPRPLPFPRPGPRPIP 71.6 7 (bac7, cow RPLPFPRPGPRPIPRPLPFPRPGPRPIPRPL cathelicidin)

APOO2OO P21564, Mastoparan B LKLKSIWSWAKKWL 717 (MP-B, insect, XXA) APOOOO5 P21663, Andropin WFIDILDKVENAIHNAAOVGIGFAKPF 718 (insect, fly) EKLINPK APOOOO8 P22226, Cyclic RLCRIWWIRWCR 719 dodecapeptide (cow cathelicidin)

APO12O5 P23826, Lactocin S STPWLASWAWSMELLPTASWLYSDWA. 72 O (XXD3, bacteria) GCFKYSAKHHC

APOO239 P24335, XPF (the GWASKIGOTLGKIAKWGLKELIOPK 721 Xenopsin precursor fragment, African clawed frog) APOO235 P25068, Bovine tracheal NPVSCVRNKGICVPIRCPGSMKOIGTC 722 antimicrobial peptide WGRAWKCCRKK (TAP, cow) APOO418 P2523 O. CAP18 (rabbit GLRKRLRKFRNKIKEKLKKIGOKIOGF 723 cathelicidin, BBL) WPKLAPRTDY APOO2O3 P25403, MJ-AMP1 OCIGNGGRCNENVGPPYCCSGFCLRO 724 (MAMP1, plant PGOGYGYCKNR defensin) APOO2O2 P25404, MJ-AMP2 CIGNGGRCNENVGPPYCCSGFCLROP 72 (MAMP2, plant NOGYGVCRNR defensin) APOO138 P28310, Cryptdin-3 LRDLWCYCRKRGCKRRERMINGTCRK 726 (Crp3, animal defensin, GHLMYTLCCR alpha, mouse) APOO184 P28794, MBP-1 (plant) RSGRGECRROCLRRHEGOPWETOEC 727 MRRCRRRG

APOOO5 O P29 OO2, Bombinin-like GIGASILSAGKSALKGLAKGLAEHFAN 728 peptide 1 (BLP-1, toad) US 2010/0316643 A1 Dec. 16, 2010 54

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOOO51 P29 OO3, Bombinin-like GIGSAILSAGKSALKGLAKGLAEHFAN 729 peptide 2 (BLP-2, toad)

APOOO52 P29004, Bombinin-like GIGAAILSAGKSALKGLAKGLAEHF 73 O peptide 3 (BLP-3, XXA, toad) APOOO53 P29 OO5, Bombinin-like GIGAAILSAGKSIIKGLANGLAEHF 731 peptide 4 (BLP-4, toad) APOO 634 P2943 O. Pediocin PA-1/ KYYGNGWTCGKHSCSWDWGKATTCII 732 AcH (PedPA1 class IIA NNGAMAWATGGHOGNHKC bacteriocin, bacteria) APOO2O4 P29559, Nisin Z ITSISLCTPGCKTGALMGCNMIKTATC 733 (lantibiotic, class I NCSIHWSK bacteriocin, bacteria) APOO13 O P29561, Cecropin C GWLKKLGKRIERIGQHTRDATIOGLGI 734 (insect, fly) AQQAANVAATAR

APOOOO1 P31107, GLWSKIKEWGKEAAKAAAKAAGKAA 73 ADENOREGULIN LGAWSEAW (Dermaseptin B2, Dermaseptin-B2, DRS B2, DRS B2, frog) APOO228 P31529, Sapecin B LTCEIDRSLCLLHCRLKGYLRAYCSQQ 736 (insect, flesh fly) KVCRCVO APOO229 P31530, Sapecin C ATCDLLSGIGWOHSACALHCVFRGNR 737 (insect, flesh fly) GGYCTGKGICWCRN APOO218 P32.195, Protegrin 2 RGGRLCYCRRRFCICW 738 (PG-2, pig cathelicidin) APOO 219 P321.96, Protegrin 3 RGGGLCYCRRRFCWCWGR 739 (PG-3, pig cathelicidin) APOOO73 P32412, Brewinin-1E FLPLLAGLAANFLPKIFCKITRKC 74 O (frog)

APOOO8 O P32414, Esculentin-1 GIFSKLGRKKIKNLLISGLKNWGKEWG 74.1 (frog) MDWWRTGIDIAGCKIKGEC

APOOO74 P32423. Brewinin-1 FLPWLAGIAAKWWPALFCKITKKC 742 (frog)

APOOO75 P32424 Brewinin-2 GLLDSLKGFAATAGKGVLOSLLSTAS 743 (frog) CKLAKTC

APOO175 P34084, Macaque DSHEERHHGRHGHHKYGRKFHEKHH 744 histatin (M-Histatin 1, SHRGYRSNYLYDN primate, monkey) APOOOO6 P35581, Apiidaecin IA GNNRPVYIPOPRPPHPRI 74. (insect, honeybee) APOOOO 7 P35581, Apiidaecin IB GNNRPVYIPOPRPPHPRL 746 (insect, honeybee) APOO414 P3 619 O Ceratotoxin A SIGSALKKALPWAKKIGKIALPIAKAA 747 (insect, fly) LP APOO 415 P3 61.91, Ceratotoxin B SIGSAFKKALPWAKKIGKAALPIAKAA 748 (insect, fly) LP

APOO172 P36193, Drosocin GKPRPYSPRPTSHPRPIRW 749 (insect)

US 2010/0316643 A1 Dec. 16, 2010 58

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No

APOO257 P5 6242, Caerin 4.1 GLWOKIKSAAGDLASGIVEGIKS 813 (frog)

APOO258 P5 6243, Caerin 4.2 GLWOKIKSAAGDLASGIVEAIKS 814 (frog)

APOO259 P5 6244, Caerin 4.3 GLWOKIKNAAGDLASGIVEGIKS 815 (frog)

APOO434 P5 6249 Frenatin 3 GLMSWLGHAWGNWLGGLFKS 816 (frog)

APOO272 P56386, Murine beta- DOYKCLOHGGFCLRSSCPSNTKLOGT 817 defensin. 1 (m3D-1, CKPDKPNCCKS mouse)

APOO368 P56425, BMAP-34 GLFRRLRDSIRRGQQKILEKARRIGERI 818 (BMAP34, cow KDIFRG cathelicidin)

APOO273 P56685, Buthinin SIWPIRCRSNRDCRRFCGFRGGRCTYA 819 (Sahara scorpion) ROCLCGY

APOO282 P56872, SIPCGESCWFIPCTWTALLGCSCKSKWC 82O Cyclopsychotride A YKN (CPT, plant cyclotides, XXC) APOOO94 P56917, Temporin A FLPLIGRWLSGIL 821 (XXA, frog) APOOO96 P56918, Temporin C LLPILGNLLNGLI 822 (XXA, frog) APOOO97 P56920, Temporin E WLPIIGNLLNSLL 823 (XXA, frog) APOOO98 P56921, Temporin F FLPLIGKWLSGIL 824 (XXA, frog) APOO 100 P56923, Temporin K LLPNLIKSTL 825 (XXA, frog) APOO295 P56928 eNAP-2 (horse) EWERKHPLGGSRPGRCPTWPPGTFGHC 826 ACLCTGDASEPKGOKCCSN APOO101 P57104, Temporin L FWOWFSKFLGRIL 827 (XXA, frog) APOOO95 P79874, Temporin B LLPIWGNLLKSLL 828 (XXA, frog) APOoog 9 P79875, Temporin G FFPWIGRILNGIL 829 (XXA, frog) APOO413 P80032, Coleoptericin SLOGGAPNFPOPSQQNGGWOWSPDLG 83 O (insect) RDDKGNTRGOIEIONKGKDHDFNAG WGKWIRGPNKAKPTWHWGGTYRR

APOO396 P8 OO54, PR-39 (PR39, RRRPRPPYLPRPRPPPFFPPRLPPRIPPG 831 pig cathelicidin) FPPRFPPRFP APOO182 P8 O154. Insect defensin GFGCPLDOMOCHRHCOTITGRSGGYC 832 SGPLKLTCTCYR

APOO444 P80223, Cortico statin GICACRRRFCLNFEOFSGYCRVNGAR 833 WI (CS-WI) (animal YVRCCSRR defensin rabbit)

US 2010/0316643 A1 Dec. 16, 2010 65

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOO3O1 P82656, Hadrurin GILDTIKSIASKVWNSKTVODLKRKGI 964 (scorpion) NWWANKLGVSPQAA

APOO113 P8274 O, GLISGLKKWGKHWAKNWAWSIMDSL 965 RANATUERIN 1.T KCKISGDC (frog)

APOO114 P82741, SMLSVLKNLGKVGLGFWACKINKOC 966 RANATUERIN 1. (Ranatuerin-1, frog)

APOO115 P82742, GLFLDTLKGAAKDWAGKLEGLKCKIT 96.7 RANATUERIN 2 GCKLP (Ranatuerin-2, frog)

APOO116 P8278 O. GFLDI INKLGKTFAGHMLDKIKCTIGT 96.8 RANATUERIN 3 CPPSP (Ranatuerin-3, frog)

APOO117 P82819, FLPFIARLAAKWFPSIICSWTKKC 96.9 RANATUERIN 4 (Ranatuerin-4, frog)

APOO 405 P82821, FISAIASMLGKFL 97 O RANATUERIN 6 (frog)

APOO4O6 P82822, FISAIASMLGKFL 971. RANATUERIN 7 (frog)

APOO4O7 P82823, FISAIASFLGKFL 972 RANATUERIN 8 (frog)

APOO 408 P82824, FLFPLITSFLSKWL 973 RANATUERIN 9 (frog) APOO461 P82825, Brewinin-1LA FLPMLAGLAASMWPKLWCLITKKC 974. (frog)

APOO462 P82826, Brewinin-1LB FLPMLAGLAASMWPKFWCLITKKC 97. (frog)

APOO118 P82828, GILDSFKGWAKGWAKDLAGKLLDKLK 976 RANATUERIN 2La CKITGC (Ranatuerin-2Lla, frog)

APOO119 P82829, GILSSIKGVAKGVAKNWAAOLLDTLK 977 RANATUERIN 2Lo CKITGC (Ranatuerin-2Lb frog) APOO109 P8283 O, Temporin-1 La WLPLISMALGKLL 978 (Temporin 1La, frog) APOO110 P82831, Temporin-1 Lib NFLGTLINLAKKIM 979 (Temporin 1Lib, frog)

APOO111 P82832, Temporin-1Lic FLPILINLIHKGLL 98 O (Temporin 1Lic, frog)

APOO463 P82833, Brewinin-1BA FLPFIAGMAAKFLPKIFCAISKKC 981 (frog)

APOO464 P82834, Brewinin-1BB FLPAIAGMAAKFLPKIFCAISKKC 982 (frog)

APOO465 P82835, Brewinin-1BC FLPFIAGWAAKFLPKIFCAISKKC 983 (frog)

APOO466 P82836, Brewinin-1BD FLPAIAGWAAKFLPKIFCAISKKC 984 (frog)

US 2010/0316643 A1 Dec. 16, 2010 70

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOO431 Ref, human LLP 1 RVIEWVOGACRAIRHIPRRIROGLERIL O76

APOO432 Ref, human LLP RIAGYGLRGLAWIIRICIRGLNLIFEIIR O77 APOO447 Ref, Anoplin (insect) GLLKRIKTLL O78 APOO474 Ref, Piscidin 3 (fish) FIHHIFRGIWHAGRSIGRFLTG O79

APOO481 Ref, Kaliocin-1 FFSASCVPGADKGOFPNLCRLCAGTG O8O (synthetic) ENKCA

APOO482 Ref. Thionin mutation KSCCRNTWARNCYNWCRLPGTISREIC O81 (synthetic) AKKCRCKIISGTTCPSDYPK APOO484 Ref, Stomoxyn (insect, RGFRKHFNKLWKKWKHTISETAHWAK O82 fly) DTAWIAGSGAAWWAAT APOO486 Ref, Cupiennin 1b GFGSLFKFLAKKVAKTWAKOAAKOG O83 (spider) AKYIANKOME APOO487 Ref, Cupiennin 1c GFGSLFKFLAKKVAKTWAKOAAKOG O84 (spider) AKYIANKOTE APOO488 Ref, Cupiennin 1D GFGSLFKFLAKKVAKTWAKOAAKOG O85 (spider) AKYWANKHME APOO489 Ref, Hipposin (fish) SGRGKTGGKARAKAKTRSSRAGLQFP O86 WGRVHRLLRKGNYAHRWGAGAPWYL

APOO923 Ref, Carnobacteriocin AISYGNGVYCNKEKCWVNKAENKOA O87 B1 (XXO, class IIa ITGIWIGGWASSLAGMGH bacteriocin, bacteria) APOO496 Ref, HP 2-2O (synthetic) AKKVFKRLEKLFSKIONDK O88 APOO497 Ref Maximin H5 (toad) ILGPWLGLWSDTLDDWIGIL O89

APOO498 Ref, rCRAMP (rat GLVRKGGEKEGEKLRKIGOKIKEFFO O90 cathelicidin) KLALEIEQ APOO500 Ref, S9-P18 (synthetic) KWKLFKKISKFLHLAKKF O91 APOO5O1 Ref, L9-P18 (synthetic) KWKLFKKILKFLHLAKKF O92 APOO502 Ref, Clavaspirin (sea FLRFIGSWIHGIGHLWHHIGWAL O93 squirt, tunicate)

APOO503 Ref, human P-113D AKRHHGYKRKFH O94

APOO504 Ref, human MUC7 20- LAHOKPFIRKSYKCLHKRCR O95 Mer APOO507 Ref, Nigrocin 2 (frog) GLISKWLGWGKKWICGWSGLC O96 APOO 508 Ref, Nigrocin 1 (frog) GLLDSIKGMAISAGKGALONLLKVAS O97 CKLDKTC

APOO509 Ref, human Calcitermin WAIALKAAHYHTHKE O98 APOO510 Ref, Dicynthaurin (sea ILOKAVLDCLKAAGSSLSKAAITAIYN O99 peach) KIT

APOO 511 Ref KIGAKI KIGAKIKIGAKIKIGAKI 1 OO (synthetic) APOO516 Ref, Lycotoxin I IWLTALKFLGKHAAKHLAKOOLSKL 1 O1 (spider)

APOO517 Ref, Lycotoxin II KIKWFKTMKSIAKFIAKEOMKKHLGGE 1 O2 (spider) US 2010/0316643 A1 Dec. 16, 2010 71

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No

APOO 518 Ref, Ib-AMP3 (plant OYRHRCCAWGPGRKYCKRWC O3 defensin, balsam) APOO519 Ref, Ib-AMP4 (plant EWGRRCCGWGPGRRYCRRWC O4 defensin, balsam) APOO521 Ref, DhvarA (synthetic) KRLFKKLLFSLRKY OS APOO522 Ref, Dhvar5 (synthetic) LLLFLLKKRKKRKY O6 APOO525 Ref Maximin H2 (toad) ILGPWLSMWGSALGGLIKKI O7

APOO526 Ref Maximin H3 (toad) ILGPWLGLWGNALGOLIKKI O8 APOO527 Ref Maximin H4 (toad) ILGPWISKIGGWLGGLLKNL O9 APOO528 Ref, Anionic peptide DDDDDD 1O SAAP (sheep) APOO530 Ref, Lantibiotic Ericin VLSKSLCTPGCITGPLOTCYLCFPTFA 11 A (bacteria) KC APOO531 Ref, Kenojeinin I (sea GKOYFPKWGGRLSGKAPLAAKTHRRL 12 skate) KP AP00532 Ref, Lunatusin (plant, KTCENLADTFRGPCFATSNC 13 ZZHp) APOO533 Ref, Fallaxin (frog) GWWDILKGAAKDIAGHLASKWMNKL 14

APOO534 Ref, Tu-AMP 2 KSCCRNTTARNCYNWCRIPG 15 (TuAMP2, thionin-like antimicrobial peptides, plant defensin, tulip) APOO535 Ref, Pilosulin 1 (Myr b GLGSWFGRLARILGRWIPKWAKKLGPK 1116 I) (Australian ants) VAKVLPKVMKEAIPMAVEMAKSOEE QQPQ APOO536 Ref, Luxuriosin (insect) SVRTODNAVNROIFGSNGPYRDFOLS 1117 DCYLPLETNPYCNEWOFAYHWNNAL MDCERAIYHGCNRTRNNFITLTACKN OAGPICNRRRH APOO537 Ref, SAMP H1 (fish, AEWAPAPAAAAPAKAPKKKAAAKPK 18 Atlantic salmon) KAGPS

APOO538 Ref, Halocidin (dimer WLNALLHHGLNCAKGWLA 19 Hall18 + Hall15) (tunicate)

APOO539 Ref AOD (American GFGCPWNRYOCHSHCRSIGRLGGYCA 2O oyster defensin, animal GSLRLTCTCYRS defensin) APOO540 Ref, Pentadactylin GLL.DTLKGAAKNWWGSLASKWMEKL 21 (frog) APOO541 Ref, Polybia-MPI IDWKKLLDAAKOIL 22 (insect, social Wasp) APOO542 Ref, Polybia-CP (insect, ILGTILGLLKSL 23 social Wasp) APOO543 Ref, Ocellatin-1 (XXA, GWWDILKGAGKDLLAHLWGKISEKW 24 frog)

APOO544 Ref, Ocellatin-2 (XXA, GVLDIFKDAAKOILAHAAEKOI 25 frog) US 2010/0316643 A1 Dec. 16, 2010 72

TABL E 10 - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http: aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence

APOO545 Ref, Ocellatin-3 (frog) GVLDILKNAAKNILAHAAEOI 1126

APOO548 Ref, CMAP 27 (chicken RFGRFLRKIRRFRPKVTITIOGSARFG 1127 myeloid antimicrobial peptide 27, bird cathelicidin, chicken cathelicidin)

APOOSSO Ref, Tu-AMP-1 KSCCRNTWARNCYNWCRIPGTPRPVC 1128 (TuAMP 1, thionin-like AATCDCKLITGTKCPPGYEK antimicrobial peptides, plant defensin, tulip)

APOO551 Ref, Combi-2 FRWWHR 1129 (synthetic)

APOO552 Ref, Maximin 9 (frog) GIGRKFLGGWKTTFRCGWKDFASKHLY 1130

APOO554 Reft S1 moricin (insect) GKIPWKAIKKAGAAIGKGLRAINIAST 1131 AHDWYSFFKPKHKKK

APOO555 Ref, Parasin I (catfish) KGRGKOGGKVRAKAKTRSS 1132

APOO556 Ref, Kassinatuerin-1 GFMKYIGPLIPHAWKAISDLI 1133 (frog)

APOO557 Ref, Fowlicidin-1 RWKRWWPLWIRTWIAGYNLYRAIKKK 1134 (chCATH-1, bird cathelicidin, chicken cathelicidin)

APOO559 Ref, Eryngiin ATRWWYCNRRSGSWWGGDDTWYYEG 35 (mushroom, fungi)

APOOS60 Ref, Dendrocin (plant, TTLTLHNLCPYPWWWLWTPNNGGFPII 36 bamboo) DNTPWWLG

APOO561 Ref, Coconut antifungal EOCREEEDDR 37 peptide (plant)

APOO562 Ref, Pandinin 1 (African GKVWDWIKSAAKKIWSSEPVSOLKG 38 scorpion) OVLNAAKNYWAEKIGATPT

APOOS63 Ref, White cloud bean KTCENLADTFRGPCFATSNCDDHCKN 39 defensin (plant KEHLLSGRCRDDFRCWCTRNC defensin)

APOO564 Ref, Dybowskin-1 FLIGMTHGLICLISRKC 4 O (frog)

APOOS65 Ref, Dybowskin-2 FLIGMTOGLICLITRKC 41 (frog)

APOO566 Ref, Dybowskin-3 GLFDWWKGVLKGWGKNWAGSLLEOL 42 (frog) KCKLSGGC

APOO567 Ref, Dybowskin- 4 WWPLGLWICKALKIC 43 (frog)

APOO568 Ref, Dybowskin-5 GLFSWWTGWLKAWGKNWAKNWGGSL 44 (frog) LEOLKCKKISGGC

APOO569 Ref, Dybowskin- 6 FLPLLLAGLPLKLCFLFKKC 45 (frog)

APOOSFO Ref, Pleurain-A1 (frog) SIITMTKEAKLPQLWKOIACRLYNTC 46

APOO571 Ref, Pleurain-A2 (frog) SIITMTKEAKLPQSWKOIACRLYNTC 47 US 2010/0316643 A1 Dec. 16, 2010 73

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOO574. Ref, Esculentin-IGRa GLFSKFAGKGIKNLIFKGWKHIGKEWG 48 (frog) MDWIRTGIDWAGCKIKGEC

APOO575 Ref, Brewinin-2GRa GLLDTFKNLALNAAKSAGWSWLNSLS 49 (frog) CKLSKTC

APOO576 Ref, Brewinin-2GRb GVLGTWKNLLIGAGKSAAOSVLKTLS SO (frog) CKLSNDC

APOO577 Ref, Brewinin-2GRc GLFTLIKGAAKLIGKTWAKEAGKTGLE 51 (frog) LMACKITNOC

APOO578 Ref, Brewinin-1GRa FLPLLAGLAANFLPKIFCKITKKC 52 (frog) APOO579 Ref, Nigrocin-2GRa GLISGILGAGKHIWCGLSGIC 53 (frog) APOO580 Ref, Nigrocin-2GRb GLFGKILGWGKKWICGLSGMC 54 (frog) APOO581 Ref, Nigrocin-2GRc GLISGILGAGKNIWCGLSGIC 55 (frog)

APOO582 Ref, Brewinin-2GHa GFSSLFKAGAKYLLKSVGKAGAQOLA 56 (frog) CKAANNCA

APOO583 Ref, Brewinin-2GHb GWITDALKGAAKTWAAELLRKAHCKL st (frog) TNSC APOO 584 Ref, Guentherin (frog) WIDDLKKWAKKWRRELLCKKHHKKLN 58

APOO585 Ref, Brewinin-2GHo SIWEGIKNAGKGFLWSILDKWRCKWA 59 (frog) GGCNP APOO586 Ref, Temporin-GH FLPLLFGAISHLL 60 (frog)

APOO587 Ref, Brewinin-2TSa GIMSLFKGVLKTAGKHWAGSLVDOLK 61 (frog) CKITGGC

APOO588 Ref, Brewinin-1TSa FLGSIWGALASALPSLISKIRN 62 (frog) APOO589 Ref, Temporin-1TSa FLGALAKIISGIF 63 (frog)

APOO593 Ref, Brewinin-1CSa FLPILAGLAAKIWPKLFCLATKKC 64 (frog) APOO594 Ref, Temporin-1CSa FLPIWGKLLSGLL 65 (frog) APOO595 Ref, Temporin-1CSb FLPIIGKLLSGLL 66 (frog) APOO 596 Ref, Temporin-1CSc FLPLWTGLISGLL 67 (frog) APOO597 Ref, Temporin-1CSd NFLGTLWNLAKKIL 68 (frog) APOO598 Ref, Temporin-1SPb FLSAITSLLGKLL 69 (frog)

APOO599 Ref, Brewinin-2-related GIWDTIKSMGKVFAGKILONL 70 (frog)

APOO6OO Ref, Odorranain-HP GLILRASSWWGRKYYWDLAGCAKA 71. (frog)

US 2010/0316643 A1 Dec. 16, 2010 75

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No

APOO638 Ref, Citropin 2.1 (frog) GLIGSIGKALGGLLWDWLKPKL 195 APOO 639 Ref, Citropin 2.1.3 GLIGSIGKALGGLLVDVLKPKLOAAS 196 (frog)

APOO64 O Ref Maculatin 1.3 GLIGLLGSWWSHWWPAIWGHF 197 (frog)

APOO641 Ref, Pardaxin 1 GFFALIPKIISSPLFKTLLSAWGSALSSS 198 (Pardaxin P-1, Pardaxin GEOE P1, Pa1, flat fish) APOO642 Ref, Pardaxin 2 GFFALIPKIISSPIFKTLLSAWGSALSSS 199 (Pardaxin P-2, Pardaxin GGOE P2, Pa2, flat fish) APOO643 Ref, Pardaxin 3 GFFAFIPKIISSPLFKTLLSAWGSALSSS 2 OO (Pardaxin P-3, Pardaxin GEOE P3, Pa3 flat fish) APOO645 Ref, Pardaxin 5 GFFAFIPKIISSPLFKTLLSAWGSALSSS 2O1 (Pardaxin P-5 Pardaxin GDOE P5, Pa5 flat fish) APOO647 Ref, Brewinin-1PLb FLPLIAGLAANFLPKIFCAITKKC 2O2 (frog)

APOO648 Ref, Brewinin-1PLc FLPWIAGWAAKFLPKIFCAITKKC 2O3 (frog)

APOO649 Ref, Esculentin-1PLa GLFPKINKKKAKTGWFNIIKTWGKEAG 2O4. (frog) MDLIRTGIDTIGCKIKGEC

APOO 650 Ref, Esculentin-1PLb GIFTKINKKKAKTGWFNIIKTIGKEAG 2O5 (frog) MDWIRAGIDTISCKIKGEC

APOO651 Ref, Esculentin-2PLa GLFSILKGWGKIALKGLAKNMGKMGL 2O6 (frog) DLWSCKISKEC

APOO652 Ref, Ranatuerin-2PLa GIMDTVKNVAKNLAGOLLDKLKCKIT 2O7 (frog) AC

APOO653 Ref, Ranatuerin-2PLb GIMDTWKNAAKDLAGOLLDKLKCRIT 2O8 (frog) GC

APOO654 Ref, Ranatuerin-2PLc GLLDTIKNTAKNLAWGLLDKIKCKMT 209 (frog) GC

APOO655 Ref, Ranatuerin-2PLd GIMDSVKNVAKNIAGOLLDKLKCKIT 210 (frog) GC

APOO656 Ref, Ranatuerin-2PLe GIMDSVKNAAKNLAGOLLDTIKCKIT 211 (frog) AC

APOO657 Ref, Ranatuerin-2PLf GIMDTVKNAAKDLAGOLDKLKCRITGC 212 (frog)

APOO658 Ref, Temporin-1PLa FLPLWGKILSGLI 213 (frog)

APOO659 Ref, Ranatuerin 5 (frog) FLPIASLIGKYL 214

APOO661 Ref, Esculentin-2L GILSLFTGGIKALGKTLFKMAGKAGA 215 (frog) EHLACKATNOC

APOO662 Ref, Esculentin-2B GLFSILRGAAKFASKGIGKDLTKLGW 216 (ESC2B-RANBE, frog) DLVACKISKOC US 2010/0316643 A1 Dec. 16, 2010 76

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOO663 Ref, Esculentin-2P GFSSIFRGWAKFASKGIGKDLARLGW 217 (frog) NLVACKISKOC APOO664 Ref, Peptide A1 (frog) FLPAIAGILSQLF 218 APOO665 Ref, Peptide B9 (frog) FLPLIAGLIGKLF 219 APOO666 Ref, PG-L (frog) EGGGPOWAVGHFM 22O APOO667 Ref, PG-KI (frog) EPHPDEFWGLM 221 APOO668 Ref, PG-KII (frog) EPNPDEFWGLM 222 APOO669 Ref, PG-KIII (frog) EPHPNEFWGLM 223 APOO67O Ref, PG-SPI (frog) EPNPDEFFGLM 224 APOO66O Ref, Pandinin 2 (African FWGALAKGALKLIPSLFSSFSKIKD 225 scorpion) APOO671 Ref, PG-SPII (frog) EPNPNEFFGLM 226 APOO673 Ref, Lantibiotic Eric in S WKSESVCTPGCVTGVLOTCFLOTITC 227 (bacteria NCHISK

APOO674 Ref, Lantibiotic Ericin VLSKSLCTPGCITGPLOTCYLCFPTFA 228 A (bacteria KC

APOO675 Ref. Human beta FELDRICGYGTARCRKKCRSOEYRIGR 229 defensin 4 (HBD-4, CPNTYACCLRKWDESLLNRTKP HBD4, human defensin)

APOO676 Ref, RL-37 (RL37, RLGNFFRKVKEKIGGGLKKWGOKIKD 23 O monkey cathelicidin) FLGNLWPRTAS APOO677 Ref, CAP11 (Guinea pig GLRKKFRKTRKRIOKLGRKIGKTGRK 231 cathelicidin) WWKAWREYGOIPYPCRI APOO678 Ref, Canine cathelicidin RLKELITTGGOKIGEKIRRIGORIKDFF 232 (K9CATH) (dog) KNLOPREEKS APOO679 Ref, Esculent in 2WEb GLFSILKGWGKIAIKGLGKNIGKMGL 233 (frog) DLWSCKISKEC

APOO680 Ref, SMAP-34 (sheep GLFGRLRDSLORGGOKILEKAERIWC 234 cathelicidin) KIKDIFR APOO681 Ref, OaBac5 (sheep RFRPPIRRPPIRPPFRPPFRPPWRPPIRPP 235 cathelicidin) FRPPFRPPIGPFP APOO682 Ref, OaBac6 (sheep RRLRPRHOHFPSERPWPKPLPLPLPRP 236 cathelicidin) GPRPWPKPLPLPLPRPGLRPWPKPL APOO683 Ref, OaBac7.5 (sheep RRLRPRRPRLPRPRPRPRPRPRSLPLPR 237 cathelicidin) POPRRIPRPILLPWRPPRPIPRPOIOPIPR WL

APOO684 Ref, OaBac11 (sheep RRLRPRRPRLPRPRPRPRPRPRSLPLPR 238 cathelicidin) PKPRPIPRPLPLPRPRPKPIPRPLPLPRP RPRRIPRPLPLPRPRPRPIPRPLPLPOPO PSPIPRPL

APOO 685 Ref, Ranatuerin 2WEb GIMDTWKGWAKTWAASLLDKLKCKIT 1239 (frog) GC

APOO 686 Ref, eCATH-1 (horse KRFGRLAKSFLRMRILLPRRKILLAS 124 O cathelicidin) APOO 687 Ref, eCATH-2 (horse KRRHWFPLSFOEFLEOLRRFRDOLPFP 1241 cathelicidin) US 2010/0316643 A1 Dec. 16, 2010 77

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No

APOO 688 Ref, eCATH-3 (horse KRFHSVGSLIORHOOMIRDKSEATRH 242 cathelicidin) GIRIITRPKLLLAS APOO689 Ref, Prophenin-1 (pig AFPPPNWPGPRFPPPNFPGPRFPPPNFP 243 cathelicidin) GPRFPPPNFPGPRFPPPNFPGPPFPPPIFP GPWFPPPPPFRPPPFGPPRFP APOO690 Ref, Prophenin-2 (pig AFPPPNWPGPRFPPPNWPGPRFPPPNFP 244 cathelicidin) GPRFPPPNFPGPRFPPPNFPGPPFPPPIFP GPWFPPPPPFRPPPFGPPRFP APOO691 Ref, HFIAP-1 (hagfish GFFKKAWRKWKHAGRRWLDTAKGW 245 cathelicidin) GRHYWNNWLNRYR APOO692 Ref, HFIAP-3 (hagfish GWFKKAWRKWKNAGRRWLKGWGIH 246 cathelicidin) YGWGLI

APOO693 Ref, Trout cath (fish RICSRDKNCVSRPGWGSIIGRPGGGSLI 247 cathelicidin) GRPGGGSWIGRPGGGSPPGGGSFNDEF IRDHSDGNRFA

APOO694 Ref, MRP (melittin- AIGSILGALAKGLPTLISWIKNR 248 related peptide) APOO695 Ref, Temporin-1TGa FLPILGKLLSGIL 249 (frog) APOO696 Ref, Dahlein 1.1 (frog) GLFDIIKNIWSTL 250 APOO697 Ref, Dahlein 1.2 (frog) GLFDIIKNIFSGL 251 APOO698 Ref, Dahlein 4.1 (frog) GLWOLIKDKIKDAATGFWTGIOS 252 APOO699 Ref, Dahlein 4.2 (frog) GLWQFIKDKLKDAATGLVTGIOS 253 APOO7OO Ref, Dahlein 4.3 (frog) GLWOFIKDKFKDAATGLVTGIOS 254 APOO 701 Ref, Dahlein 5.1 (frog) GLIGSIGNAIGAFIANKLKP 255 APOO 702 Ref, Dahlein 5. 2 (frog) GLIGSIGNAIGAFIANKLKPK 256 APOO 703 Ref, Dahlein 5.3 (frog) GLLASLGKWIGGYLAEKLKP 27 APOO 704 Ref, Dahlein 5. 4 (frog) GLIGSIGKWIGGYLAEKLKPK 258 APOO 705 Ref, Dahlein 5.5 (frog) GLLASLGKWIGGYLAEKLKPK 259 APOO 706 Ref, Dahlein 5.6 (frog) GLLASLGKWFGGYLAEKLKPK 26 O APOO 709 Ref, Mytilus defensin GFGCPNDYPCHRHCKSIPGRAGGYCG 261 (mytilin) A. (mollusc) GAHRLRCTCYR

APOO711 Ref Mussel defensin GFGCPNNYACHOHCKSIRGYCGGYC 262 MGD2 AGWFRLRCTCYRCG

APOO712 Ref, scorpion defensin GFGCPLNOGACHRHCRSIRRRGGYCA 263 GFFKQTCCYRN

APOO713 Ref, Androctonus GFGCPFNOGACHRHCRSIRRRGGYCA 264 defensin GLFKQTCTCYR

APOO714. Ref. Orinthodoros GYGCPFNOYOCHSHCSGIRGYKGGYC 265 defensin A (soft ticks) KGTFKOTCKCY APOO715 Ref, VaD1 (plant RTCMKKEGWGKCLIDTTCAHSCKNR 266 defensin) GYGGNCKGMTRTCYCLVNC APOO722 Ref, Cryptonin (insect, GLINGLALRLGKRALKKIIKRLCR 267 cicada) US 2010/0316643 A1 Dec. 16, 2010 78

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No

APOO723 Ref, Decoralin (insect) SLLSLLRKLIT 1268

APOO724 Ref, RTD-2 (rhesus RCLCRRGWCRCLCRRGWC 1269 theta-defensin-2, minidefensin, XXC BBS lectin, ZZHa) APOO725 Ref, RTD-3 (rhesus RCICTRGFCRCICTRGFC 1270 theta-defensin-3, minidefensin, XXC BBS lectin, ZZHa)

APOO726 Ref, Combi-1 RRWWRF 271 (synthetic) APOO748 Ref, Gm pro-rich pept1 DIOIPGIKKPTHRDIIIPNWNPNVRTOP 272 (insect) WORFGGNKS APOO749 Ref, Gm anionic pept 1 EADEPLWLYKGDNIERAPTTADHPILP 273 (insect) SIIDDWKLDPNRRYA APOO750 Ref, Gm pro-rich pept 2 EIRLPEPFRFPSPTWPKPIDIDPILPHPWS 274 (insect) PROTYPIIARRS

APOO752 Ref Gm defensin-like DKLIGSCWWGATNYTSDCNAECKRR 27s peptide (insect) GYKGGHCGSFWNVNCWCEE

APOO753 Ref Gm VOETOKLAKTVGANLEETNKKLAPOI 276 apolipophoricin (insect) KSAYDDFWKQAQEWQKKLHEAASKO APOO754 Ref, Gm anionic pept2 ETESTPDYLKNIOOOLEEYTKNFNTOV 277 (insect) ONAFDSDKIKSEVNNFIESLGKILNTE KKEAPK

APOO755 Ref, Gm cecropin D- ENFFKEIERAGORIRDAIISAAPAVETL 278 like pept, insect AQAOKIIKGGD APOO756 Ref, Dermaseptin-B6 ALWKDILKNAGKAALNEINOLVNQ 279 (DRS-B6, DRS B6, XXA, frog)

APOO759 Ref, Phylloseptin-O1 FLSLIPHAINAVSTLWHHSG 28O (PLS-O1, Phylloseptin 4, PS- 4, XXA, frog) APOO 760 Ref, Phylloseptin-O2 FLSLIPHAINAWSAIAKHS 281 (PLS-O2, Phylloseptin 5, PS-5, XXA, frog) APOO761 Ref, Phylloseptin- 6 SLIPHAINAWSAIAKHF 282 (Phylloseptin-H4, PLS H4, PS-6, XXA, frog) APOO762 Ref, Phylloseptin-7 FLSLIPHAINAWSAIAKHF 283 (Phylloseptin-H5, PLS H5, PS-7, XXA, frog) APOO 763 Ref, Dermaseptin DPh-1 GLWSTIKNWGKEAAIAAGKAAL.GAL 284 (XXA, frog) APOO764 Ref, Dermaseptin-S9 GLRSKIWLWWLLMIWOESNKFKKM 285 (DRS-S9, DRS S9, frog) APOO 765 Ref. Human salvic MHDFWWLWWLLEYIYNSACSWLSATS 286

US 2010/0316643 A1 Dec. 16, 2010 80

TABLE 1 O - continued Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps. unmc.edu/APA main.php).

SEQ ID Effector Structure/Sequence No APOO789 Ref, NRC-15 (XXA, GFWGKLFKLGLHGIGLLHLHL 3 O9 fish, gene predicted)

APOO 790 Ref, NRC-16 (XXA, GWKKWLRKGAKHLGOAAIK 310 fish, gene predicted)

APOO 791 Ref, NRC-17 (XXA, GWKKWLRKGAKHLGOAAIKGLAS 311 fish, gene predicted)

APOO792 Ref, NRC-19 (XXA, FIGLLFHGWHHWGKWIHGLIHGHH 312 fish, gene predicted) APOO793 Ref, Bombinin H2 IIGPWLGLWGSALGGLIKKI 313 (XXA, frog) APOO794 Ref, Bombinin H3 (frog, IIGPWLGMWGSALGGLIKKI 314 XXD, XXA) APOO795 Ref, Bombinin H7 (frog, ILGPILGLWSNALGOLL 315 XXD, XXA) APOO796 Ref, Bombinin GH-1L, IIGPWLGLWGKPLESLLE 316 (XXA, toad) APOO797 Ref, Bombinin GH-1D IIGPWLGLWGKPLESLLE 317 (toad, XXD, XXA) APOO807 Ref, Enterocin E-76O NRWYCNSAAGGWGGAAGCWLAGYW 3.18 (bacteriocin, bacteria) GEAKENIAGEWRKGWGMAGGFTHNK ACKSFPGSGWASG APOO808 Ref, hepcidin (fish) CRFCCRCCPRMRGCGLCCRF 319 APOO809 Ref, hepcidin TH1-5 GIKCRFCCGCCTPGICGVCCRF 32O (fish) APOO810 Ref, hepcidin TH2-3 OSHLSLCRWCCNCCRSNKGC 321 (fish)

APOO811 Ref, human LEAP-2 MTPFWRGWSLRPIGASCRDDSECITRL 322 CRKRRCSLSWAOE APOO812 Ref, Enkelytin (cow) FAEPLPSEEEGESYSKEPPEMEKRYGG 323 FM

APOO732 Ref, Spheniscin-1 SFGLCRLRRGSCAHGRCRFPSIPIGRCS 324 (Sphe-1, avian defensin) RFVOCCRRVW APOO733 Ref, Organgutan LLGDFFRKAREKIGEEFKRIVORIKDFL 3.25 ppyLL-37 (Great Ape, RNLWPRTES primate cathelicidin) APOO734 Ref, Gibbon himdSL-37 SLGNFFRKARKKIGEEFKRIVORIKDF 326 (hylobatidae, primate LOHLIPRTEA cathelicidin) APOO735 Ref, pobRL-37 RLGNFFRKAKKKIGRGLKKIGOKIKDF 327 (cercopithecidae, GNLWPRTES primate cathelicidin) APOO736 Ref, caRL-37 (primate RLGDILOKAREKIEGGLKKLWOKIKDF 328 cathelicidin) FGKFAPRTES

APOO 737 Ref, Plastic in PBN2KF GLWTSLIKGAGKLIGGLFGSWTG 329 (XXA, DRP-PBN2, frog)

APOO738 Ref, Plasticin ANCKF GLWTGLLKTAGKLIGDLFGSLTG 330 (XXA, synthetic)