Synthesis and evaluation of pseudopeptide analogues of a specific CXCR4 inhibitor, T140:: The insertion of an (E)-alkene dipeptide isostere into the βII′-turn moiety

被引：36

作者：

Tamamura, H ^{[1
]}

Hiramatsu, K

Miyamoto, K

Omagari, A

Oishi, S

Nakashima, H

Yamamoto, N

Kuroda, Y

Nakagawa, T

Otaka, A

Fujii, N

机构：

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan

[2] St Marianna Univ, Sch Med, Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan

[3] Tokyo Med & Dent Univ, Sch Med, Bunkyo Ku, Tokyo 1138519, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 06期

关键词：

D O I：

10.1016/S0960-894X(02)00041-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A 14-residue peptide, T140, strongly inhibits the T-cell line-tropic HIV-1 (X4-HIV-1) infection, since this peptide functions as a specific antagonist against a chemokine receptor, CXCR4. T140 takes an antiparallel beta-sheet structure with a type II' P-turn. In the present paper, we have designed and synthesized several T140 analogues in which an (E)-alkene dipeptide isostere was inserted into the type II' beta-turn moiety, as a bridging study to develop nonpeptidic CXCR4 inhibitors. It has been proven that the turn region of T140 can be replaced by the above surrogate with the maintenance of strong anti-HIV activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：923 / 928

页数：6

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