期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 19, 期 1, 页码 91-101出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.11.049
关键词
HIV; gp120; CD4; Entry inhibitor; Virtual screening; Docking; Shape-based similarity
资金
- NIH [GM 56550]
- Japan Society for the Promotion of Science
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI024755, ZIAAI005023] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P01GM056550] Funding Source: NIH RePORTER
The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor and is therefore an important lead in the development of a potent viral entry inhibitor. Reported here is the use of two orthogonal screening methods, GOLD docking and ROCS shape-based similarity searching, to identify amine-building blocks that, when conjugated to the core scaffold, yield novel analogs that maintain similar affinity for gp120. Use of this computational approach to expand SAR produced analogs of equal inhibitory activity but with diverse capacity to enhance viral infection. The novel analogs provide additional lead scaffolds for the development of HIV-1 entry inhibitors that employ protein-ligand interactions in the vestibule of gp120 Phe 43 cavity. (C) 2010 Elsevier Ltd. All rights reserved.
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