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

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

doi:10.1039/B812029C

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

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

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^a Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, Japan
E-mail: tsutsumi.mr@tmd.ac.jp, tamamura.mr@tmd.ac.jp
Fax: 813 5280 8039
Tel: 813 5280 8036

^b Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan

^c AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan

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.

Organic & Biomolecular Chemistry

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

Abstract

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

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