Dimerization inhibitors of HIV-1 protease

被引：44

作者：

Boggetto, N

Reboud-Ravaux, M

机构：

[1] Univ Paris 06, Inst Jacques Monod, Dept Biol Cellulaire, Lab Enzymol Mol & Fonct,CNRS,UMR 7592, F-75251 Paris 05, France

[2] Univ Paris 07, Inst Jacques Monod, Dept Biol Cellulaire, Lab Enzymol Mol & Fonct,CNRS,UMR 7592, F-75251 Paris, France

来源：

BIOLOGICAL CHEMISTRY | 2002年 / 383卷 / 09期

关键词：

AIDS; dimerization inhibitors; HIV-1; protease; interface peptides; lipopeptides; molecular hairpins;

D O I：

10.1515/BC.2002.150

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

By targeting the highly conserved antiparallel beta-sheet formed by the interdigitation of the N and C-terminal strands of each monomer, dimerization inhibitors of HIV-1 protease may be useful to overcome the drug resistance observed with current active-site directed antiproteases. Sequestration of the monomer by the inhibitor (or disruption of the dimer interface) prevents the correct assembly of the inactive monomers to active enzyme. Strategies for the design of drugs targeting the dimer interface are described. Various dimerization inhibitors are reported including N- and C-terminal mimetics, lipopeptides and crosslinked interface peptides.

引用

页码：1321 / 1324

页数：4

共 29 条

[1] SYNTHETIC INTERFACE PEPTIDES ALTER DIMERIC ASSEMBLY OF THE HIV-1 AND HIV-2 PROTEASES
BABE, LM
ROSE, J
CRAIK, CS
[J]. PROTEIN SCIENCE, 1992, 1 (10) : 1244 - 1253
[2] Design, synthesis, and evaluation of conformationally constrained tongs, new inhibitors of HIV-1 protease dimerization
Bouras, A
Boggetto, N
Benatalah, Z
de Rosny, E
Sicsic, S
Reboud-Ravaux, M
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (06) : 957 - 962
[3] Design of dimerization inhibitors of HIV-1 aspartic proteinase: A computer-based combinatorial approach
Caflisch, A
Schramm, HJ
Karplus, M
[J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2000, 14 (02) : 161 - 179
[4] Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance
Carr, A
Samaras, K
Chisholm, DJ
Cooper, DA
[J]. LANCET, 1998, 351 (9119) : 1881 - 1883
[5] DISSOCIATION AND ASSOCIATION OF THE HIV-1 PROTEASE DIMER SUBUNITS - EQUILIBRIA AND RATES
DARKE, PL
JORDAN, SP
HALL, DL
ZUGAY, JA
SHAFER, JA
KUO, LC
[J]. BIOCHEMISTRY, 1994, 33 (01) : 98 - 105
[6] TOWARD IMPROVED ANTI-HIV CHEMOTHERAPY - THERAPEUTIC STRATEGIES FOR INTERVENTION WITH HIV-INFECTIONS
DECLERCQ, E
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (14) : 2491 - 2517
[7] DUMOND J, 2001, 2 GEN M INT PROT SOC
[8] Inhibition of HIV-1 protease by a subunit of didemnaketal A
Fan, XD
Flentke, GR
Rich, DH
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (34) : 8893 - 8894
[9] A SYSTEMATIC EVALUATION OF THE INHIBITION OF HIV-1 PROTEASE BY ITS C-TERMINAL AND N-TERMINAL PEPTIDES
FRANCISKOVICH, J
HOUSEMAN, K
MUELLER, R
CHMIELEWSKI, J
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (04) : 765 - 768
[10] COMPARATIVE-ANALYSIS OF THE SEQUENCES AND STRUCTURES OF HIV-1 AND HIV-2 PROTEASES
GUSTCHINA, A
WEBER, IT
[J]. PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1991, 10 (04): : 325 - 339

← 1 2 3 →