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
Organic & Biomolecular Chemistry Pub Date : 10/17/2008 00:00:00 , DOI:
10.1039/B812029CAbstract
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.
