Structure-activity relationship study of CXCR4 antagonists bearing the cyclic pentapeptide scaffold: identification of the new pharmacophore.
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.
Tanaka
Tomohiro
T
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, 101-0062, Japan.
Tsutsumi
Hiroshi
H
Nomura
Wataru
W
Tanabe
Yasuaki
Y
Ohashi
Nami
N
Esaka
Ai
A
Ochiai
Chihiro
C
Sato
Jun
J
Itotani
Kyoko
K
Murakami
Tsutomu
T
Ohba
Kenji
K
Yamamoto
Naoki
N
Fujii
Nobutaka
N
Tamamura
Hirokazu
H
D000818:Animals; D002417:Cattle; D002460:Cell Line; D055808:Drug Discovery; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry
D009842:Oligopeptides; D010456:Peptides, Cyclic; D019718:Receptors, CXCR4; D014443:Tyrosine