Cyclic Adenosine Monophosphate : a Study of Four- and Five-Coordinated Phosphorus Compounds, Modelling the Activated State of Camp
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Chapter 23 Nucleic Acids
7-9/99 Neuman Chapter 23 Chapter 23 Nucleic Acids from Organic Chemistry by Robert C. Neuman, Jr. Professor of Chemistry, emeritus University of California, Riverside [email protected] <http://web.chem.ucsb.edu/~neuman/orgchembyneuman/> Chapter Outline of the Book ************************************************************************************** I. Foundations 1. Organic Molecules and Chemical Bonding 2. Alkanes and Cycloalkanes 3. Haloalkanes, Alcohols, Ethers, and Amines 4. Stereochemistry 5. Organic Spectrometry II. Reactions, Mechanisms, Multiple Bonds 6. Organic Reactions *(Not yet Posted) 7. Reactions of Haloalkanes, Alcohols, and Amines. Nucleophilic Substitution 8. Alkenes and Alkynes 9. Formation of Alkenes and Alkynes. Elimination Reactions 10. Alkenes and Alkynes. Addition Reactions 11. Free Radical Addition and Substitution Reactions III. Conjugation, Electronic Effects, Carbonyl Groups 12. Conjugated and Aromatic Molecules 13. Carbonyl Compounds. Ketones, Aldehydes, and Carboxylic Acids 14. Substituent Effects 15. Carbonyl Compounds. Esters, Amides, and Related Molecules IV. Carbonyl and Pericyclic Reactions and Mechanisms 16. Carbonyl Compounds. Addition and Substitution Reactions 17. Oxidation and Reduction Reactions 18. Reactions of Enolate Ions and Enols 19. Cyclization and Pericyclic Reactions *(Not yet Posted) V. Bioorganic Compounds 20. Carbohydrates 21. Lipids 22. Peptides, Proteins, and α−Amino Acids 23. Nucleic Acids ************************************************************************************** -
List of Abbreviations
List of Abbreviations 1,3BPGA 1,3-Bisphospho-D-glycerate 10-formyl THF 10-Formyltetrahydrofolate 2PG 2-phospho-D-glycerate 3PG 3-phospho-D-glycerate 3PPyr 3-phosphonooxypyruvate 3PSer 3-phosphoserine 6PDG 6-phospho-D-gluconate 6Pgl glucono-1,5-lactone-6-phosphate AcAcACP acetoacetyl-ACP AcAcCoA acetoacetyl-CoA AcACP acetyl-ACP AcCoA acetyl-CoA ACP acyl carrier protein ADP adenosine 5'-diphosphate AKG alpha-ketoglutarate Ala alanine AMP adenosine 5'-monophosphate Arg arginine ArgSuc argininosuccinate Asn asparagine Asp aspartate ATP adenosine 5'-triphosphate CDP cytidine 5'-diphosphate Chol cholesterol Ci citrulline Cit citrate CMP cytidine 5'-monophosphate CO2 carbon dioxide CoA coenzyme A CP carbamoyl-phosphate CTP cytidine 5'-triphosphate Cytc-ox ferricytochrome c Cytc-red ferrocytochrome c dADP 2'-deoxyadenosine 5'-diphosphate dAMP 2'-deoxyadenosine 5'-monophosphate dCDP 2'-deoxycytosine 5'-diphosphate dCMP 2'-deoxycytosine 5'-monophosphate dGDP 2'-deoxyguanosine 5'-diphosphate dGMP 2'-deoxyguanosine 5'-monophosphate DHAP dihydroxyacetone phosphate DHF 7,8-Dihydrofolate dTMP 2'-Deoxythymidine-5'-monophosphate dUDP 2'-Deoxyuridine-5'-diphosphate dUMP 2'-Deoxyuridine-5'-monophosphate Ery4P erythrose-4-phosphate F16BP fructose 1,6-bisphosphate F6P fructose 6-phosphate FAD flavin adenine dinucleotide FADH2 flavin adenine dinucleotide reduced for formate fPP farnesyl diphosphate Fum fumarate G6P glucose 6-phosphate GA guanidinoacetate GA3P glyceraldehyde 3-phosphate GDP guanosine 5'-diphosphate Glc glucose Gln glutamine Glu glutamate GluSA -
Inhibition by Cyclic Guanosine 3':5'-Monophosphate of the Soluble DNA Polymerase Activity, and of Partially Purified DNA Polymer
Inhibition by Cyclic Guanosine 3':5'-Monophosphate of the Soluble DNA Polymerase Activity, and of Partially Purified DNA Polymerase A (DNA Polymerase I) from the Yeast Saccharomyces cere visiae Hans Eckstein Institut für Physiologische Chemie der Universität, Martinistr. 52-UKE, D-2000 Hamburg 20 Z. Naturforsch. 36 c, 813-819 (1981); received April 16/July 2, 1981 Dedicated to Professor Dr. Joachim Kühnauon the Occasion of His 80th Birthday cGMP, DNA Polymerase Activity, DNA Polymerase A, DNA Polymerase I, Baker’s Yeast DNA polymerase activity from extracts of growing yeast cells is inhibited by cGMP. Experiments with partially purified yeast DNA polymerases show, that cGMP inhibits DNA polymerase A (DNA polymerase I from Chang), which is the main component of the soluble DNA polymerase activity in yeast extracts, by competing for the enzyme with the primer- template DNA. Since the enzyme is not only inhibited by 3',5'-cGMP, but also by 3',5'-cAMP, the 3': 5'-phosphodiester seems to be crucial for the competition between cGMP and primer. This would be inconsistent with the concept of a 3'-OH primer binding site in the enzyme. The existence of such a site in the yeast DNA polymerase A is indicated from studies with various purine nucleoside monophosphates. When various DNA polymerases are compared, inhibition by cGMP seems to be restricted to those enzymes, which are involved in DNA replication. DNA polymerases with an associated nuclease activity are not inhibited, DNA polymerase B from yeast is even activated by cGMP. Though some relations between the cGMP effect and the presumed function of the enzymes in the living cell are apparent, the biological meaning of the observations in general remains open. -
Triphosphate Accumulation, DNA Damage, and Growth Inhibition Following Exposure to CB3717 and Dipyridamole Nicola J
(CANCER RESEARCH 51. 2346-2352, May I. 1991) Mechanism of Cell Death following Thymidylate Synthase Inhibition: 2'-Deoxyuridine-5'-triphosphate Accumulation, DNA Damage, and Growth Inhibition following Exposure to CB3717 and Dipyridamole Nicola J. Curtin,1 Adrian L. Harris, and G. Wynne Aherne Cancer Research L'nil, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne [N. J. C.J; Imperial Cancer Research Fund Clinical Oncology Unit, Churchill Hospital, Headington, Oxon ¡A.L. H.]; Department of Biochemistry, University of Surrey, Guildford, Surrey [G. W. A.], England ABSTRACT but one hypothesis, based on the study of bacterial mutants (3- The thymidylate synthasc inhibitor /V'°-propargyl-5,8-dideazafolic 5), is that TS inhibition leads not only to a reduction in dTTP levels but also, as dUMP accumulates behind the block, to the acid (CB3717) inhibits the growth of human lung carcinoma A549 cells. formation of dUTP. The levels of dUTP eventually overwhelm The cytotoxicity of CB3717 is potentiated by the nucleoside transport inhibitor dipyridamole (DP), which not only inhibits the uptake and dUTPase (the enzyme which breaks down dUTP to dUMP) therefore salvage of thymidine but also inhibits the efflux of deoxyuridine, and the levels of dUTP increase. DNA polymerase can utilize thereby enhancing the intracellular accumulation of deoxyuridine nucleo- dUTP and dTTP with equal efficiency (6), such that uracil is tides. Measurement of intracellular deoxyuridine triphosphate (dUTP) misincorporated into DNA. Uracil in DNA is excised rapidly pools, by sensitive radioimmunoassay, demonstrated a large increase in by uracil glycosylase, leaving an apyrimidinic site. During repair response to CB3717, in a dose- and time-related manner, and this of apyrimidinic sites, in the presence of unbalanced dUTP/ accumulation was enhanced by coincubation with DP. -
Questions with Answers- Nucleotides & Nucleic Acids A. the Components
Questions with Answers- Nucleotides & Nucleic Acids A. The components and structures of common nucleotides are compared. (Questions 1-5) 1._____ Which structural feature is shared by both uracil and thymine? a) Both contain two keto groups. b) Both contain one methyl group. c) Both contain a five-membered ring. d) Both contain three nitrogen atoms. 2._____ Which component is found in both adenosine and deoxycytidine? a) Both contain a pyranose. b) Both contain a 1,1’-N-glycosidic bond. c) Both contain a pyrimidine. d) Both contain a 3’-OH group. 3._____ Which property is shared by both GDP and AMP? a) Both contain the same charge at neutral pH. b) Both contain the same number of phosphate groups. c) Both contain the same purine. d) Both contain the same furanose. 4._____ Which characteristic is shared by purines and pyrimidines? a) Both contain two heterocyclic rings with aromatic character. b) Both can form multiple non-covalent hydrogen bonds. c) Both exist in planar configurations with a hemiacetal linkage. d) Both exist as neutral zwitterions under cellular conditions. 5._____ Which property is found in nucleosides and nucleotides? a) Both contain a nitrogenous base, a pentose, and at least one phosphate group. b) Both contain a covalent phosphodister bond that is broken in strong acid. c) Both contain an anomeric carbon atom that is part of a β-N-glycosidic bond. d) Both contain an aldose with hydroxyl groups that can tautomerize. ___________________________________________________________________________ B. The structures of nucleotides and their components are studied. (Questions 6-10) 6._____ Which characteristic is shared by both adenine and cytosine? a) Both contain one methyl group. -
Cancer Science Standard Abbreviations List
Cancer Science Standard Abbreviations List Common abbreviations, acronyms and short names are listed below. These shortened forms can be used without definition in articles published in Cancer Science. The same form is used in the plural. 7-AAD 7-amino-actinomycin D (stain) ES cell embryonic stem cell Ab antibody EST expressed sequence tag ADP adenosine 5′-diphosphate FACS fluorescence-activated cell sorter dADP 2′-deoxyadenosine 5′-diphosphate FBS fetal bovine serum AIDS acquired immunodeficiency syndrome FCS fetal calf serum Akt protein kinase B FDA Food and Drug Administration AML acute myelogenous leukemia FISH fluorescence in situ hybridization AMP adenosine 5′-monophosphate FITC fluorescein isothiocyanate dAMP 2′-deoxyadenosine 5′-monophosphate FPLC fast protein liquid chromatography ANOVA analysis of variance FRET fluorescence resonance energy transfer ATCC American Type Culture Collection GAPDH glyceraldehyde-3-phosphate dehydrogenase ATP adenosine 5′-triphosphate GDP guanosine 5′-diphosphate dATP 2′-deoxyadenosine 5′-triphosphate dGDP 2′-deoxyguanosine 5′-diphosphate beta-Gal, β-Gal beta-galactosidase GFP green fluorescent protein bp base pair(s) GMP guanosine 5′-monophosphate BrdU 5-bromodeoxyuridine dGMP 2′-deoxyguanosine 5′-monophosphate BSA bovine serum albumin GST glutathione S-transferase CCK-8 Cell Counting Kit-8 (tradename) GTP guanosine 5′-triphosphate CDP cytidine 5′-diphosphate dGTP 2′-deoxyguanosine 5′-triphosphate cCDP 2′-deoxycytidine 5′-diphosphate HA hemagglutinin CHAPS 3-[(3-cholamidopropyl)dimethylamino]-1- -
Chem 109 C Bioorganic Compounds
Chem 109 C Bioorganic Compounds Fall 2019 HFH1104 Armen Zakarian Office: Chemistry Bldn 2217 http://labs.chem.ucsb.edu/~zakariangroup/courses.html CLAS Instructor: Dhillon Bhavan [email protected] Midterm 3 stats Average 49.1 St Dev 14.1 Max 87.5 Min 15 test are available outside room 2135 (Chemistry, 2nd floor) in a box, sorted in alphabetical order, by color Final Course Grading Each test will be curved individually to 75% average Lowest midterm will be dropped Scores from 2 best M and the Final will be added Grades will be assigned according to the syllabus 22. Draw all reactions required to convert hexanoic acid to 3 molecules of acetyl CoA through 11 pt the β-oxidation cycles. Name all necessary coenzymes and enzymes. How many molecules of ATP and CO2 will be produced from hexanoic acid after its entire metabolism through all 4 stages ? O O hexanoic acid (hexanoate) Overview OVERVIEW o structures of DNA vs. RNA - ribose o structures of bases: Adenine, Uracil/Thymine, Guanine, Cytosine. “Enol forms” o hydrogen bonding between A-T(U) and G-C. H-donors/acceptors o Base complementarity o RNA strand cleavage assisted by the 2’-OH group in the ribose unit (cyclic PDE) o Deamination: RNA genetic instability o DNA replication o RNA synthesis: transcription. Template strand (read 3’ to 5’). Sense strand and the RNA primary structure (T −> U). o Protein synthesis: translation. mRNA determines the amino acid sequence. tRNAs are amino acid carriers. rRNA - part of ribosomes o no section 26.12, 26.13 DNA, RNA, etc. -
Modeling of the Hydration Shell of Uracil and Thymine
Int. J. Mol. Sci. 2000, 1, 17-27 International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.org/ijms/ Modeling of the Hydration Shell of Uracil and Thymine Oleg V. Shishkin1,2, Leonid Gorb2 and Jerzy Leszczynski2* 1Department of Alkali Halide Crystals, Institute for Single Crystals, National Academy of Sciences of Ukraine, 60 Lenina Avenue., Kharkiv 310001, Ukraine 2Computational Center for Molecular Structure and Interactions, Department of Chemistry, Jackson State University, P.O. Box 17910, 1325 Lynch Street, Jackson, MS 39217, USA E-mail: [email protected] *Author to whom correspondence should be addressed. Received: 4 January 2000 / Accepted: 30 March 2000 / Published: 4 March 2000 Abstract: The molecular geometry of complexes of uracil and thymine with 11 water mole- cules was calculated using the density functional theory with the B3LYP functional. The standard 6-31G(d) basis set has been employed. It was found that the arrangement of water molecules forming a locked chain around the nucleobases significantly differs for uracil and thymine. The presence of a methyl group in thymine results in strong non-planarity of the hydrated shell. The existence of C-H...O hydrogen bonds between the water molecules and the hydrophobic part of the nucleobases is established. Interactions with water molecules cause some changes in the geometry of uracil and thymine which can be explained by the contribution of a zwitter-ionic dihydroxy resonance form into the total structure of the molecules. Keywords: Uracil, Thymine, Hydration, Molecular structure, Hydrogen bonds, Density functional theory. Introduction Since Franklin and Gosling [1] examined the first fibers of DNA it has been known that DNA oc- curs in vivo in the hydrated form. -
Distribution of Nucleosides in Populations of Cordyceps Cicadae
Molecules 2014, 19, 6123-6141; doi:10.3390/molecules19056123 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Distribution of Nucleosides in Populations of Cordyceps cicadae Wen-Bo Zeng 1, Hong Yu 1,*, Feng Ge 2, Jun-Yuan Yang 1, Zi-Hong Chen 1, Yuan-Bing Wang 1, Yong-Dong Dai 1 and Alison Adams 3 1 Yunnan Herbal Laboratory, Institute of Herb Biotic Resources, Yunnan University, Kunming 650091, Yunnan, China; E-Mails: [email protected] (W.-B.Z.); [email protected] (J.-Y.Y.); [email protected] (Z.-H.C.); [email protected] (Y.-B.W.); [email protected] (Y.-D.D.) 2 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, China; E-Mail: [email protected] 3 Department of Biological Sciences, College of Engineering, Forestry and Natural Science, Northern Arizona University, Flagstaff, AZ 86011-5640, USA; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected] or [email protected]; Tel.: +86-137-006-766-33; Fax: +86-871-650-346-55. Received: 15 January 2014; in revised form: 25 April 2014 / Accepted: 5 May 2014 / Published: 14 May 2014 Abstract: A rapid HPLC method had been developed and used for the simultaneous determination of 10 nucleosides (uracil, uridine, 2'-deoxyuridine, inosine, guanosine, thymidine, adenine, adenosine, 2'-deoxyadenosine and cordycepin) in 10 populations of Cordyceps cicadae, in order to compare four populations of Ophicordyceps sinensis and one population of Cordyceps militaris. Statistical analysis system (SAS) 8.1 was used to analyze the nucleoside data. -
Deoxyadenosine Triphosphate As a Mediator of Deoxyguanosine Toxicity in Cultured T Lymphoblasts
Deoxyadenosine triphosphate as a mediator of deoxyguanosine toxicity in cultured T lymphoblasts. G J Mann, R M Fox J Clin Invest. 1986;78(5):1261-1269. https://doi.org/10.1172/JCI112710. Research Article The mechanism by which 2'-deoxyguanosine is toxic for lymphoid cells is relevant both to the severe cellular immune defect of inherited purine nucleoside phosphorylase (PNP) deficiency and to attempts to exploit PNP inhibitors therapeutically. We have studied the cell cycle and biochemical effects of 2'-deoxyguanosine in human lymphoblasts using the PNP inhibitor 8-aminoguanosine. We show that cytostatic 2'-deoxyguanosine concentrations cause G1-phase arrest in PNP-inhibited T lymphoblasts, regardless of their hypoxanthine guanine phosphoribosyltransferase status. This effect is identical to that produced by 2'-deoxyadenosine in adenosine deaminase-inhibited T cells. 2'-Deoxyguanosine elevates both the 2'-deoxyguanosine-5'-triphosphate (dGTP) and 2'-deoxyadenosine-5'-triphosphate (dATP) pools; subsequently pyrimidine deoxyribonucleotide pools are depleted. The time course of these biochemical changes indicates that the onset of G1-phase arrest is related to increase of the dATP rather than the dGTP pool. When dGTP elevation is dissociated from dATP elevation by coincubation with 2'-deoxycytidine, dGTP does not by itself interrupt transit from the G1 to the S phase. It is proposed that dATP can mediate both 2'-deoxyguanosine and 2'-deoxyadenosine toxicity in T lymphoblasts. Find the latest version: https://jci.me/112710/pdf Deoxyadenosine Triphosphate as a Mediator of Deoxyguanosine Toxicity in Cultured T Lymphoblasts G. J. Mann and R. M. Fox Ludwig Institute for Cancer Research (Sydney Branch), University ofSydney, Sydney, New South Wales 2006, Australia Abstract urine of PNP-deficient individuals, with elevation of plasma inosine and guanosine and mild hypouricemia (3). -
CFA As a Clinically Translatable Probe for PET Imaging of Deoxycytidine Kinase Activity
[18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity Woosuk Kima,b,1, Thuc M. Lea,b,1, Liu Weia,b, Soumya Poddara,b, Jimmy Bazzya,b, Xuemeng Wanga,b, Nhu T. Uonga,b, Evan R. Abta,b, Joseph R. Capria,b, Wayne R. Austinc, Juno S. Van Valkenburghb,d, Dalton Steeleb,d, Raymond M. Gipsond, Roger Slavika,b, Anthony E. Cabebea,b, Thotsophon Taechariyakula,b, Shahriar S. Yaghoubie, Jason T. Leea,f, Saman Sadeghia,b, Arnon Lavieg, Kym F. Faulla,b,h,i, Owen N. Wittea,j,k,l, Timothy R. Donahuea,b,m, Michael E. Phelpsa,f,2, Harvey R. Herschmana,b,n, Ken Herrmanna,b, Johannes Czernina,b, and Caius G. Radua,b,2 aDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; bAhmanson Translational Imaging Division, University of California, Los Angeles, CA 90095; cAbcam, Cambridge, MA 02139-1517; dDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095; eCellSight Technologies, Inc., San Francisco, CA 94107; fCrump Institute for Molecular Imaging, University of California, Los Angeles, CA 90095; gDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607; hThe Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095; iDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095; jDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, CA 90095; kHoward Hughes Medical Institute, University of California, Los Angeles, CA 90095; lEli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095; mDepartment of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and nDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 Contributed by Michael E. -
Developmental Disorder Associated with Increased Cellular Nucleotidase Activity (Purine-Pyrimidine Metabolism͞uridine͞brain Diseases)
Proc. Natl. Acad. Sci. USA Vol. 94, pp. 11601–11606, October 1997 Medical Sciences Developmental disorder associated with increased cellular nucleotidase activity (purine-pyrimidine metabolismyuridineybrain diseases) THEODORE PAGE*†,ALICE YU‡,JOHN FONTANESI‡, AND WILLIAM L. NYHAN‡ Departments of *Neurosciences and ‡Pediatrics, University of California at San Diego, La Jolla, CA 92093 Communicated by J. Edwin Seegmiller, University of California at San Diego, La Jolla, CA, August 7, 1997 (received for review June 26, 1997) ABSTRACT Four unrelated patients are described with a represent defects of purine metabolism, although no specific syndrome that included developmental delay, seizures, ataxia, enzyme abnormality has been identified in these cases (6). In recurrent infections, severe language deficit, and an unusual none of these disorders has it been possible to delineate the behavioral phenotype characterized by hyperactivity, short mechanism through which the enzyme deficiency produces the attention span, and poor social interaction. These manifesta- neurological or behavioral abnormalities. Therapeutic strate- tions appeared within the first few years of life. Each patient gies designed to treat the behavioral and neurological abnor- displayed abnormalities on EEG. No unusual metabolites were malities of these disorders by replacing the supposed deficient found in plasma or urine, and metabolic testing was normal metabolites have not been successful in any case. except for persistent hypouricosuria. Investigation of purine This report describes four unrelated patients in whom and pyrimidine metabolism in cultured fibroblasts derived developmental delay, seizures, ataxia, recurrent infections, from these patients showed normal incorporation of purine speech deficit, and an unusual behavioral phenotype were bases into nucleotides but decreased incorporation of uridine.