Inhibitory profile of a LEDGF/p75 peptide against HIV-1 integrase: Insight into integrase-DNA complex formation and catalysis

被引：48

作者：

Al-Mawsawi, Laith Q. ^{[1
]}

Christ, Frauke ^{[2
,3
]}

Dayam, Raveendra ^{[1
]}

Debyser, Zeger ^{[2
,3
]}

Neamati, Nouri ^{[1
]}

机构：

[1] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA

[2] Katholieke Univ Leuven, Lab Mol Virol & Gene Therapy, B-3000 Louvain, Belgium

[3] IRC KULAK, B-3000 Louvain, Belgium

来源：

FEBS LETTERS | 2008年 / 582卷 / 10期

关键词：

HIV-1; integrase; cellular cofactor; LEDGF/p75; peptide; peptidomimetic;

D O I：

10.1016/j.febslet.2008.02.076

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：

A lens epithelium-derived growth factor ( LEDGF)/p75 peptide was evaluated for human immunodeficiency virus type 1 integrase ( IN) inhibitory activity. The LEDGF/p75 peptide modestly inhibited IN catalysis and was dependent on IN DNA assembly. The peptide was also effective at disrupting LEDGF/p75-IN complex formation. We next investigated the activity of the LEDGF/p75 peptide on IN mutant proteins that are unable to catalyze the DNA strand transfer reaction. The LEDGF/p75 peptide displayed an increased potency on these IN proteins, from 5-fold to greater than 10-fold, indicating the IN multimeric state greatly influences the peptide inhibitory effects. These results shed light on IN-DNA multimeric formation, and how this process influences the LEDGF/p75-IN interaction. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：1425 / 1430

页数：6

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