带有环五肽骨架的CXCR4拮抗剂的构效关系研究：新药效团的鉴定

Structure-activity relationship study of CXCR4 antagonists bearing the cyclic pentapeptide scaffold: identification of the new pharmacophore.

作者信息

Tanaka Tomohiro, Tsutsumi Hiroshi, Nomura Wataru, Tanabe Yasuaki, Ohashi Nami, Esaka Ai, Ochiai Chihiro, Sato Jun, Itotani Kyoko, Murakami Tsutomu, Ohba Kenji, Yamamoto Naoki, Fujii Nobutaka, Tamamura Hirokazu

机构信息

Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, 101-0062, Japan.

出版信息

Org Biomol Chem. 2008 Dec 7;6(23):4374-7. doi: 10.1039/b812029c. Epub 2008 Oct 17.

DOI:10.1039/b812029c

PMID:19005596

Abstract

A highly potent CXCR4 antagonist 2 [cyclo (-D-Tyr1-Arg2-Arg3-Nal4-Gly5-)] has previously been identified by screening cyclic pentapeptide libraries that were designed based on pharmacophore residues of a 14-residue peptidic CXCR4 antagonist 1. In the present study, D-Tyr and Arg in peptide 2 were replaced by a bicyclic aromatic amino acid and a cationic amino acid, respectively, and their binding activity for CXCR4 was evaluated for identification of the novel pharmacophore.

摘要

一种高效的CXCR4拮抗剂2 [环(-D-酪氨酸1-精氨酸2-精氨酸3-萘丙氨酸4-甘氨酸5-)] 先前已通过筛选基于14个氨基酸的肽类CXCR4拮抗剂1的药效团残基设计的环五肽文库而被鉴定出来。在本研究中，肽2中的D-酪氨酸和精氨酸分别被双环芳香族氨基酸和阳离子氨基酸取代，并评估了它们对CXCR4的结合活性，以鉴定新的药效团。