The structure of an HIV-1 specific cell entry inhibitor in complex with the HIV-1 gp41 trimeric core.

Bioorg Med Chem
Authors
Keywords
Abstract

The three-dimensional structure of the complex between an HIV-1 cell-entry inhibitor selected from screening a combinatorial library of non-natural building blocks and the central, trimeric, coiled-coil core of HIV-1 gp41 has been determined by X-ray crystallography. The biased combinatorial library was designed to identify ligands binding in nonpolar pockets on the surface of the coiled-coil core of gp41. The crystal structure shows that the non-peptide moiety of the inhibitor binds to the targeted cavity in two different binding modes. This result suggests a strategy for increasing inhibitor potency by use of a second-generation combinatorial library designed to give simultaneous occupancy of both binding sites.

Year of Publication
2000
Journal
Bioorg Med Chem
Volume
8
Issue
9
Pages
2219-27
Date Published
2000 Sep
ISSN
0968-0896
PubMed ID
11026535
Links
Grant list
GM-39589 / GM / NIGMS NIH HHS / United States