PMID: 9448264Mar 14, 1998Paper

Analysis of the S3 and S3' subsite specificities of feline immunodeficiency virus (FIV) protease: development of a broad-based protease inhibitor efficacious against FIV, SIV, and HIV in vitro and ex vivo

Proceedings of the National Academy of Sciences of the United States of America
T LeeC H Wong

Abstract

The S3 and S3' subsite binding specificities of HIV and feline immunodeficiency virus proteases (FIV) proteases (PRs) have been explored by using C2-symmetric competitive inhibitors. The inhibitors evaluated contained (1S, 2R, 3R, 4S)-1,4-diamino-1, 4-dibenzyl-2,3-diol as P1 and P1' units, Val as P2 and P2' residues, and a variety of amino acids at the P3 and P3' positions. All inhibitors showed very high potency against HIV PR in vitro, and their Ki values ranged between 1.1 and 2.6 nM. In contrast to the low restriction of P3 and P3' residues observed in HIV PR, FIV PR exhibited strong preference for small hydrophobic groups at the S3 and S3' subsites. Within this series, the most effective inhibitor against FIV PR contained Ala at P3 and P3'. Its Ki of 41 nM was 415- and 170-fold lower than those of the inhibitors without the P3 and P3' moieties or with the Phe at these positions, respectively. In addition, these compounds were tested against mutant FIV PRs, which contain amino acid substitutions corresponding to those in native HIV PR at homologous sites, and their efficacy of inhibition progressively increased up to 5-fold. The most potent FIV PR inhibitor was selected for examination of its effectiveness in tissue culture...Continue Reading

References

Feb 1, 1992·AIDS Research and Human Retroviruses·C Debouck
Aug 1, 1991·Journal of Medicinal Chemistry·J R Huff
Aug 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·R L TalbottJ H Elder
Feb 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·S Tabor, C C Richardson
May 1, 1995·Nature Medicine·T W North, R A LaCasse
Jul 1, 1995·Nature Structural Biology·J W Erickson
Sep 15, 1995·The Journal of Biological Chemistry·J GroverP J Roughley
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·J P VaccaE Roth
Dec 15, 1995·The Journal of Biological Chemistry·T Ridky, J Leis
Jan 1, 1996·Annual Review of Pharmacology and Toxicology·J W Erickson, S K Burt
Apr 25, 1997·Biochimica Et Biophysica Acta·S I WilsonJ Kay
Aug 5, 1997·Chemical Reviews·Robert E. Babine, Steven L. Bender

❮ Previous
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Citations

Mar 10, 2000·Biochimica Et Biophysica Acta·A Wlodawer, A Gustchina
Sep 6, 2001·Journal of Ethnopharmacology·A C SchmittG L von Poser
Jul 13, 2002·Bioorganic & Medicinal Chemistry Letters·Sanjay K SharmaJ William Lown
Apr 3, 2003·Bioorganic & Medicinal Chemistry·Chi Ching MakChi-Huey Wong
Jun 4, 2011·Acta Crystallographica. Section D, Biological Crystallography·Ying Chuan LinC David Stout
Jul 25, 2000·Journal of Virology·R J MillerN Sarver
Sep 5, 2001·Journal of Virology·B BühlerB E Torbett
Jun 17, 2004·American Journal of Veterinary Research·Weijiang ZhangM A McCrackin Stevenson
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·C D RosinD S Goodsell
Jul 12, 2011·European Journal of Medicinal Chemistry·Maya M MakatiniThavendran Govender
Feb 22, 2008·Veterinary Immunology and Immunopathology·John H ElderYing-Chuan Lin
Sep 4, 2013·Chemical Biology & Drug Design·Theresa TiefenbrunnCharles D Stout
Jan 13, 2006·Journal of Molecular Biology·Holly HeasletC David Stout
Dec 3, 2014·Progress in Biophysics and Molecular Biology·Theresa Tiefendbrunn, C David Stout
May 1, 2010·Biochimie·Neil D Rawlings
Aug 8, 2012·European Journal of Medicinal Chemistry·Maya M MakatiniHendrik G Kruger
Jul 14, 2018·Chemical Biology & Drug Design·Siyabonga I MaphumuloHendrik G Kruger
Aug 28, 2007·Chembiochem : a European Journal of Chemical Biology·Yi-Ming ShaoChi-Huey Wong
Jan 21, 2006·Angewandte Chemie·Matthew WhitingValery V Fokin
Apr 11, 2006·Organic & Biomolecular Chemistry·Ashraf BrikChi-Huey Wong
Jul 16, 2019·Qualitative Health Research·Deborah LambotteUNKNOWN D-SCOPE Consortium
Mar 20, 2020·International Journal of Molecular Sciences·Manuela GrimaldiAnna Maria D'Ursi
Aug 24, 2013·Substance Use & Misuse·Kelly E KnightSara B Simmons
Apr 28, 2012·Attachment & Human Development·Jan N Hughes
Dec 18, 2015·Veterinary Sciences·Katrin HartmannMichèle Bergmann

❮ Previous
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