Structure-activity relationship study on artificial CXCR4 ligands possessing the cyclic pentapeptide scaffold: the exploration of amino acid residues of pentapeptides by substitutions of several aromatic amino acids

Tomohiro Tanaka; Wataru Nomura; Tetsuo Narumi; Ai Esaka; Shinya Oishi; Nami Ohashi; Kyoko Itotani; Barry J. Evans; Zi-xuan Wang; Stephen C. Peiper; Nobutaka Fujii; Hirokazu Tamamura

doi:10.1039/B908286G

Structure-activity relationship study on artificial CXCR4 ligands possessing the cyclic pentapeptide scaffold: the exploration of amino acid residues of pentapeptides by substitutions of several aromatic amino acids†

Tomohiro Tanaka,^a Wataru Nomura,*^a Tetsuo Narumi,^ab Ai Esaka,^b Shinya Oishi,^b Nami Ohashi,^a Kyoko Itotani,^a Barry J. Evans,^c Zi-xuan Wang,^cd Stephen C. Peiper,^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: nomura.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 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA

^d Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA

Abstract

Previously, downsizing of a 14-residue peptidic CXCR4 antagonist 1 has led to the development of a highly potent CXCR4 antagonist 2 [cyclo(-D-Tyr¹-Arg²-Arg³-Nal⁴-Gly⁵-)]. In the present study, cyclic pentapeptide libraries that were designed by substitutions of several amino acids for D-Tyr¹ and Arg² in peptide 2 were prepared and screened to evaluate binding activity for CXCR4. The above structure-activity relationship study led to the finding of several potent CXCR4 ligands.

Organic & Biomolecular Chemistry

Structure-activity relationship study on artificial CXCR4 ligands possessing the cyclic pentapeptide scaffold: the exploration of amino acid residues of pentapeptides by substitutions of several aromatic amino acids†

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Structure-activity relationship study on artificial CXCR4 ligands possessing the cyclic pentapeptide scaffold: the exploration of amino acid residues of pentapeptides by substitutions of several aromatic amino acids

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