A copper(I)-catalyzed 1,2,3-triazole azide-alkyne click compound is a potent inhibitor of a multidrug-resistant HIV-1 protease variant.
A copper(I)-catalyzed 1,2,3-triazole azide-alkyne click compound is a potent inhibitor of a multidrug-resistant HIV-1 protease variant.
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DOI：
10.1021/jm800149m
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发表时间：
2008-10-23
影响因子：
7.3
通讯作者：
Torbett BE
中科院分区：
文献类型：
--
作者：
Giffin MJ;Heaslet H;Brik A;Lin YC;Cauvi G;Wong CH;McRee DE;Elder JH;Stout CD;Torbett BE
Treatment with protease inhibitors, a component of Highly Active Anti-retroviral Therapy (HAART), often results in viral resistance. Structural and biochemical characterization of a 6X mutant arising from in vitro selection with compound 1, a C2-symmetric diol protease inhibitor, has been previously described. We now show that compound 2, a copper(I)-catalyzed 1,2,3-triazole derived compound previously shown to be potently effective against wild-type protease (IC50 = 6.0 nM), has low nM activity (IC50 = 15.7 nM) against the multidrug-resistant 6X HIV-1 protease mutant. Compound 2 displays similar efficacy against wild-type and 6X HIV-1 in viral replication assays. While structural studies of compound 1 bound to wild type and mutant protease revealed a progressive change in binding mode in the mutants, the 1.3 Å resolution 6X protease–compound 2 crystal structure reveals nearly identical interactions for 2 as in the wild-type protease complex with very little change in compound 2 or protease conformation.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.6
作者：
Heaslet, H;Kutilek, V;Stout, CD
通讯作者：
Stout, CD
DOI：
10.2174/1568005033481079
发表时间：
2003-12-01
期刊：
Current Drug Targets - Infectious Disorders
影响因子：
--
作者：
Kutilek, Victoria D.;Sheeter, Dennis A.;Torbett, Bruce E.
通讯作者：
Torbett, Bruce E.
DOI：
10.1590/s0036-46652005000100001
发表时间：
2005-02-01
期刊：
Revista do Instituto de Medicina Tropical de São Paulo
影响因子：
--
作者：
Machado, Daisy Maria;Fernandes, Silvana Cláudia;Diaz, Ricardo Sobie
通讯作者：
Diaz, Ricardo Sobie
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL