A SERIES OF PENICILLIN-DERIVED C2-SYMMETRICAL INHIBITORS OF HIV-1 PROTEINASE - STRUCTURAL AND MODELING STUDIES

被引：35

作者：

WONACOTT, A

COOKE, R

HAYES, FR

HANN, MM

JHOTI, H

MCMEEKIN, P

MISTRY, A

MURRAYRUST, P

SINGH, OMP

WEIR, MP

机构：

[1] GLAXO GRP RES LTD, DEPT PROT BIOCHEM, GREENFORD UB6 0HE, MIDDX, ENGLAND

[2] GLAXO GRP RES LTD, DEPT MED CHEM, GREENFORD UB6 0HE, MIDDX, ENGLAND

[3] GLAXO GRP RES LTD, PROT STRUCT GRP, GREENFORD UB6 0HE, MIDDX, ENGLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 21期

关键词：

D O I：

10.1021/jm00073a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The binding modes of a series of penicillin-derived C2 symmetric dimer inhibitors of HIV-1 proteinase were investigated by NMR, protein crystallography, and molecular modeling. The compounds were found to bind in a symmetrical fashion, tracing an S-shaped course through the active site, with good hydrophobic interactions in the S1/S1' and S2/S2' pockets and hydrogen bonding of inhibitor amide groups. Interactions with the catalytic aspartates appeared poor and the protein conformation was very similar to that seen in complexes with peptidomimetics, in spite of the major differences in ligand structure.

引用

页码：3113 / 3119

页数：7

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