Identification of small peptides inhibiting the integrase-LEDGF/p75 interaction through targeting the cellular co-factor

被引：8

作者：

Cavalluzzo, Claudia ^{[1
,2
]}

Christ, Frauke ^{[3
]}

Voet, Arnout ^{[4
,5
]}

Sharma, Ajendra ^{[1
]}

Singh, Brajendra Kumar ^{[1
,6
]}

Zhang, Kam Y. J. ^{[5
]}

Lescrinier, Eveline ^{[7
]}

De Maeyer, Marc ^{[4
]}

Debyser, Zeger ^{[3
]}

Van der Eycken, Erik ^{[1
]}

机构：

[1] Katholieke Univ Leuven, Dept Chem, LOMAC, B-3001 Louvain, Belgium

[2] DestiNA Genom Ltd, Edinburgh EH9 3JJ, Midlothian, Scotland

[3] Katholieke Univ Leuven, B-3000 Louvain, Belgium

[4] Katholieke Univ Leuven, Lab Biomol Modeling, B-3001 Louvain, Belgium

[5] RIKEN, Adv Sci Inst, Zhang Initiat Res Unit, Wako, Saitama 3510198, Japan

[6] Univ Delhi, Dept Chem, Bioorgan Lab, Delhi 110007, India

[7] Univ Leuven KU Leuven, Med Chem Lab, B-3000 Louvain, Belgium

来源：

JOURNAL OF PEPTIDE SCIENCE | 2013年 / 19卷 / 10期

关键词：

HIV; LEDGF; p75; integrase; protein-protein interaction; solid phase peptide synthesis; structure-activity relationship; SMALL-MOLECULE INHIBITORS; LEDGF/P75; BINDING-SITE; HIV-1; INTEGRASE; STRUCTURAL BASIS; PROSTATE-CANCER; DISCOVERY; PROTEIN; DOMAIN; NUCLEAR; DESIGN;

D O I：

10.1002/psc.2543

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：

The integration of the viral DNA into the host genome is one of the essential steps in the HIV replication cycle. This process is mediated by the viral enzyme integrase (IN) and lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75 has been identified as a crucial cellular co-factor of integration that acts by tethering IN to the cellular chromatin. Recently, circular peptides were identified that bind to the C-terminal domain of IN and disrupt the interaction with LEDGF/p75. Starting from the circular peptides, we identified a short peptidic sequence able to inhibit the LEDGF/p75-IN interaction at low M concentration through its binding to the IN binding site of LEDGF/p75. This discovery can lead to the synthesis of peptidomimetics with high anti-HIV activity targeting the cellular co-factor LEDGF/p75 and not the viral protein IN. Copyright (c) 2013 European Peptide Society and John Wiley & Sons, Ltd.

引用

页码：651 / 658

页数：8

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