Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part II. Integrase inhibition
SCIE
SCOPUS
- Title
- Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part II. Integrase inhibition
- Authors
- Lee-Huang, Sylvia; Huang, Philip Lin; Zhang, Dawei; Lee, Jae Wook; Bao, Ju; Sun, Yongtao; Chang, Young-Tae; Zhang, John; Huang, Paul Lee
- Date Issued
- 2007-03
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Abstract
- We report molecular modeling and functional confirmation of Ole and HT binding to HIV-1 integrase. Docking simulations identified two binding regions for Ole within the integrase active site. Region I encompasses the conserved D64-116-E152 motif, while region II involves the flexible loop region formed by amino acid residues 140-149. HT, on the other hand, binds to region II. Both Ole and HT exhibit favorable interactions with important amino acid residues through strong H-bonding and van der Waals contacts, predicting integrase inhibition. To test and confirm modeling predictions, we examined the effect of Ole and HT on HIV-1 integrase activities including 3'-processing, strand transfer, and disintegration. Ole and HT exhibit dose-dependent inhibition on all three activities, with EC(50)s in the nanomolar range. These studies demonstrate that molecular modeling of target-ligand interaction coupled with structural-activity analysis should facilitate the design and identification of innovative integrase inhibitors and other therapeutics. (c) 2007 Elsevier Inc. All rights reserved.
- Keywords
- HUMAN-IMMUNODEFICIENCY-VIRUS; ESCHERICHIA-COLI; TYPE-1; MUTATIONS; MUTANT; SITE
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/50257
- DOI
- 10.1016/j.bbrc.2007.01.058
- ISSN
- 0006-291X
- Article Type
- Article
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 354, no. 4, page. 879 - 884, 2007-03
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.