Synthesis and HIV-1 integrase inhibitory activity of dimeric and tetrameric analogs of indolicidin

被引：37

作者：

Krajewski, K

Marchand, C

Long, YQ

Pommier, Y

Roller, PP ^{[1
]}

机构：

[1] NCI, CCR, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA

[2] NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA

[3] Chinese Acad Sci, SIMM, SIBS, State Key Lab Drug Res, Shanghai 201203, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 22期

基金：

中国国家自然科学基金;

关键词：

indolicidin; integrase inhibitors; multimeric peptides;

D O I：

10.1016/j.bmcl.2004.08.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We found that indolicidin, a natural antimicrobial peptide, has HIV-1 integrase inhibitory activity. Subsequently, we also discovered analogs of indolicidin with substantially higher inhibitory potency. The dimers and tetramers of the most active sequence (ILPWKWPWWPWPP) were prepared by connection of the monomers' C-terminal ends, using lysine as a linker. The inhibitory potency of the dimeric peptide is higher than the monomeric peptide. The tetrameric peptide, prepared by connection of two dimers at C-ends using again lysine as the linker, is the most potent integrase inhibitor with IC50 value of 0.6 muM for both 3'-end processing and strand transfer. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：5595 / 5598

页数：4

共 11 条

[1] HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells [J].