دورية أكاديمية
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A Chemical Strategy for Intracellular Arming of an Endogenous Broad-Spectrum Antiviral Nucleotide.

التفاصيل البيبلوغرافية
العنوان: A Chemical Strategy for Intracellular Arming of an Endogenous Broad-Spectrum Antiviral Nucleotide.
المؤلفون: Passow KT; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States., Caldwell HS; Department of Biomedical Sciences, State University of New York at Albany School of Public Health, Albany, New York 12144, United States.; The Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York 12201, United States., Ngo KA; The Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York 12201, United States., Arnold JJ; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States., Antczak NM; Department of Health Sciences and Technology, ETH Zürich, Zürich 8092, Switzerland., Narayanan A; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States., Jose J; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.; Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, United States., Sturla SJ; Department of Health Sciences and Technology, ETH Zürich, Zürich 8092, Switzerland., Cameron CE; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States., Ciota AT; Department of Biomedical Sciences, State University of New York at Albany School of Public Health, Albany, New York 12144, United States.; The Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York 12201, United States., Harki DA; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States.
المصدر: Journal of medicinal chemistry [J Med Chem] 2021 Oct 28; Vol. 64 (20), pp. 15429-15439. Date of Electronic Publication: 2021 Oct 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington Dc : American Chemical Society
Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-
مواضيع طبية MeSH: Antiviral Agents/*pharmacology , Cytidine Triphosphate/*pharmacology , West Nile virus/*drug effects , Zika Virus/*drug effects, Animals ; Antiviral Agents/chemistry ; Cell Line ; Chlorocebus aethiops ; Cytidine Triphosphate/chemistry ; Dose-Response Relationship, Drug ; Humans ; Microbial Sensitivity Tests ; Molecular Structure ; Structure-Activity Relationship
مستخلص: The naturally occurring nucleotide 3'-deoxy-3',4'-didehydro-cytidine-5'-triphosphate ( ddhCTP ) was recently found to exert potent and broad-spectrum antiviral activity. However, nucleoside 5'-triphosphates in general are not cell-permeable, which precludes the direct use of ddhCTP as a therapeutic. To harness the therapeutic potential of this endogenous antiviral nucleotide, we synthesized phosphoramidate prodrug HLB-0532247 ( 1 ) and found it to result in dramatically elevated levels of ddhCTP in cells. We compared 1 and 3'-deoxy-3',4'-didehydro-cytidine ( ddhC ) and found that 1 more effectively reduces titers of Zika and West Nile viruses in cell culture with minimal nonspecific toxicity to host cells. We conclude that 1 is a promising antiviral agent based on a novel strategy of facilitating elevated levels of the endogenous ddhCTP antiviral nucleotide.
References: ACS Med Chem Lett. 2012 Jun 14;3(6):459-464. (PMID: 22866208)
Antimicrob Agents Chemother. 2005 May;49(5):1898-906. (PMID: 15855512)
Clin Microbiol Rev. 2016 Jul;29(3):695-747. (PMID: 27281742)
J Med Chem. 2018 Mar 22;61(6):2211-2226. (PMID: 28792763)
Curr Opin Infect Dis. 2000 Feb;13(1):5-11. (PMID: 11964766)
Protein Expr Purif. 1999 Oct;17(1):128-38. (PMID: 10497078)
J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):449-55. (PMID: 23807155)
Org Lett. 2017 May 5;19(9):2218-2221. (PMID: 28418681)
J Med Chem. 2010 Oct 14;53(19):7202-18. (PMID: 20845908)
Sci Rep. 2020 May 18;10(1):8159. (PMID: 32424333)
J Org Chem. 1973 Mar 9;38(5):990-9. (PMID: 4689159)
J Org Chem. 1971 Dec 3;36(24):3743-5. (PMID: 5315834)
Virol J. 2009 Jul 15;6:103. (PMID: 19604376)
Antiviral Res. 2017 Oct;146:161-163. (PMID: 28912011)
J Biol Chem. 2001 Jun 29;276(26):23616-23. (PMID: 11319228)
Front Mol Biosci. 2017 Nov 22;4:74. (PMID: 29214156)
Biochem Biophys Res Commun. 1991 Apr 30;176(2):586-92. (PMID: 2025274)
Org Lett. 2008 May 1;10(9):1703-6. (PMID: 18393512)
J Biol Chem. 2010 Aug 13;285(33):25602-12. (PMID: 20530478)
J Biol Chem. 2001 Nov 2;276(44):40847-57. (PMID: 11526116)
Antimicrob Agents Chemother. 2015;59(6):3563-9. (PMID: 25870059)
J Med Chem. 1999 Oct 7;42(20):4122-8. (PMID: 10514282)
J Org Chem. 2021 Jul 2;86(13):8843-8850. (PMID: 34126010)
Tetrahedron Lett. 1968 Apr;(22):2621-4. (PMID: 5646263)
Sci Rep. 2017 Jan 18;7:40920. (PMID: 28098253)
J Am Chem Soc. 2001 Feb 7;123(5):870-4. (PMID: 11456620)
ACS Med Chem Lett. 2018 Dec 20;10(1):2-5. (PMID: 30655934)
Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):1091-8. (PMID: 11562963)
Nature. 2018 Jun;558(7711):610-614. (PMID: 29925952)
J Virol Methods. 2006 Jun;134(1-2):183-9. (PMID: 16510196)
J Biol Chem. 2005 Apr 15;280(15):15356-61. (PMID: 15703176)
Bioconjug Chem. 2004 May-Jun;15(3):638-46. (PMID: 15149192)
Antiviral Res. 2020 Mar;175:104708. (PMID: 31931104)
PLoS Pathog. 2015 Jun 26;11(6):e1005009. (PMID: 26114757)
J Med Chem. 2017 Oct 12;60(19):8131-8144. (PMID: 28858511)
Expert Opin Drug Discov. 2021 Oct;16(10):1149-1161. (PMID: 33985395)
Mol Pharmacol. 1999 Oct;56(4):693-704. (PMID: 10496951)
Virology. 2005 Nov 25;342(2):252-65. (PMID: 16137736)
Protein Expr Purif. 2004 Sep;37(1):144-53. (PMID: 15294292)
Mol Pharmacol. 1987 Dec;32(6):798-806. (PMID: 2826994)
J Biol Chem. 2010 Nov 5;285(45):34337-47. (PMID: 20801890)
معلومات مُعتمدة: P30 CA077598 United States CA NCI NIH HHS; R01 AI045818 United States AI NIAID NIH HHS; R01 GM110129 United States GM NIGMS NIH HHS; R21 AI146856 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (3'-deoxy-3',4'-didehydro-CTP)
0 (Antiviral Agents)
65-47-4 (Cytidine Triphosphate)
تواريخ الأحداث: Date Created: 20211018 Date Completed: 20211208 Latest Revision: 20221029
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8877721
DOI: 10.1021/acs.jmedchem.1c01481
PMID: 34661397
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-4804
DOI:10.1021/acs.jmedchem.1c01481