Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead.


Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
11 Feb 2021
Historique:
received: 20 11 2020
accepted: 04 01 2021
entrez: 19 2 2021
pubmed: 20 2 2021
medline: 20 2 2021
Statut: epublish

Résumé

Covalent inhibitors of wild-type HIV-1 reverse transcriptase (CRTIs) are reported. Three compounds derived from catechol diether non-nucleoside inhibitors (NNRTIs) with addition of a fluorosulfate warhead are demonstrated to covalently modify Tyr181 of HIV-RT. X-ray crystal structures for complexes of the CRTIs with the enzyme are provided, which fully demonstrate the covalent attachment, and confirmation is provided by appropriate mass shifts in ESI-TOF mass spectra. The three CRTIs and six noncovalent analogues are found to be potent inhibitors with both IC

Identifiants

pubmed: 33603971
doi: 10.1021/acsmedchemlett.0c00612
pmc: PMC7883463
doi:

Types de publication

Journal Article

Langues

eng

Pagination

249-255

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM032136
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103403
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI044616
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155072
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM049551
Pays : United States
Organisme : NIH HHS
ID : S10 OD018007
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM111244
Pays : United States

Informations de copyright

© 2021 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

Références

Bioorg Med Chem. 2016 Oct 15;24(20):4768-4778
pubmed: 27485603
Ann Pharmacother. 2017 Apr;51(4):332-344
pubmed: 27895236
ACS Chem Biol. 2017 Aug 18;12(8):2015-2020
pubmed: 28718624
Mol Pharmacol. 2017 Apr;91(4):383-391
pubmed: 28167742
Angew Chem Int Ed Engl. 2017 Nov 27;56(48):15200-15209
pubmed: 28853194
Lancet HIV. 2019 Dec;6(12):e831-e859
pubmed: 31439534
Expert Opin Drug Metab Toxicol. 2019 Oct;15(10):813-829
pubmed: 31556749
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E802-E811
pubmed: 29279368
Nucleic Acids Res. 2017 Jul 3;45(W1):W331-W336
pubmed: 28444340
JAMA. 2019 May 21;321(19):1862
pubmed: 31112245
ACS Med Chem Lett. 2018 Jun 27;9(7):584-586
pubmed: 30034581
J Am Chem Soc. 2016 Jun 15;138(23):7353-64
pubmed: 27191344
Cancer Cell. 2020 Jan 13;37(1):3-4
pubmed: 31951561
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6665-70
pubmed: 15870211
Clin Microbiol Rev. 2016 Jul;29(3):695-747
pubmed: 27281742
J Am Chem Soc. 2013 Nov 6;135(44):16705-13
pubmed: 24151856
Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):9725-9730
pubmed: 28827354
J Med Chem. 2011 Dec 22;54(24):8582-91
pubmed: 22081993
Chem Sci. 2017 Feb 1;8(2):1233-1237
pubmed: 28451264
ACS Med Chem Lett. 2016 Oct 31;7(12):1156-1160
pubmed: 27994756
Spectrochim Acta A Mol Biomol Spectrosc. 2005 May;61(7):1461-70
pubmed: 15820879
ACS Med Chem Lett. 2014 Oct 13;5(11):1259-62
pubmed: 25408842
Annu Rev Med. 2019 Jan 27;70:137-150
pubmed: 30355266
Annu Rev Pharmacol Toxicol. 2015;55:249-67
pubmed: 25149918
Angew Chem Int Ed Engl. 2014 Sep 1;53(36):9430-48
pubmed: 25112519
Eur J Med Chem. 2017 Sep 29;138:96-114
pubmed: 28651155
J Am Chem Soc. 2012 Dec 5;134(48):19501-3
pubmed: 23163887
Antiviral Res. 2019 Jul;167:110-116
pubmed: 31034849

Auteurs

Joseph A Ippolito (JA)

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, United States.

Haichan Niu (H)

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.

Nicole Bertoletti (N)

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, United States.

Zachary J Carter (ZJ)

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.

Shengyan Jin (S)

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, United States.

Krasimir A Spasov (KA)

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, United States.

José A Cisneros (JA)

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.

Margarita Valhondo (M)

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.

Kara J Cutrona (KJ)

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.

Karen S Anderson (KS)

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, United States.
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520-8066, United States.

William L Jorgensen (WL)

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.

Classifications MeSH