Design, Synthesis and Activity Evaluation of Novel Bivalent HIV-1 Fusion Inhibitor

被引：2

作者：

Ling Yan-Bo ^{[1
]}

Wang Kun ^{[1
]}

Jiang Xi-Feng ^{[1
]}

Cai Li-Feng ^{[1
]}

Liu Ke-Liang ^{[1
]}

机构：

[1] Acad Mil Med Sci, Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China

来源：

CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE | 2013年 / 34卷 / 09期

关键词：

Transmembrane glycoprotein gp41; Human immunodeficiency virus (HIV); Bivalent molecule; Fusion inhibitor; Peptide; GP41; PEPTIDE; PROTEIN; LIGATION; BINDING; REGION;

D O I：

10.7503/cjcu20130391

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Multivalent inhibitor is an efficient strategy for inhibitor design based on an additive effect of Delta G. In this work, we chose C34 and T20 as the template sequences to study bivalent inhibitors targeting HIV-1 gp41 NHR domain. We optimized the crosslink sites and linkers to improve anti-HIV activities of the bivalent fusion inhibitors. Compared to monovalent molecules, significant cooperative effects in the anti-cell-cell fusion activity were observed in the bivalent inhibitors, at either N- or C-terminal crosslink of both C34 and T20. beta-Alanine may be the most suitable linker for N-terminal crosslink, while C34C is the best C-terminal crosslinked molecule. Specially, the anti-HIV IC50 value of peptide BiC beta AC34 was improved from 43. 7 nmol/L to 6. 4 nmol/L, indicating the two C-peptide chains had a cooperative effect. The results show that bivalent fusion inhibitor for gp41 design could appear a cooperative effect.

引用

页码：2102 / 2107

页数：6