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.
Previously, downsizing of a 14-residue peptidic CXCR4 antagonist has led to the development of a highly potent CXCR4 antagonist [cyclo(-d-Tyr(1)-Arg(2)-Arg(3)-Nal(4)-Gly(5)-)]. In the present study, cyclic pentapeptide libraries that were designed by substitutions of several amino acids for d-Tyr(1) and Arg(2) in peptide 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.
Tanaka
Tomohiro
T
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, 101-0062, Japan.
Nomura
Wataru
W
Narumi
Tetsuo
T
Esaka
Ai
A
Oishi
Shinya
S
Ohashi
Nami
N
Itotani
Kyoko
K
Evans
Barry J
BJ
Wang
Zi-xuan
ZX
Peiper
Stephen C
SC
Fujii
Nobutaka
N
Tamamura
Hirokazu
H
D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D008024:Ligands; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D024322:Amino Acids, Aromatic; D008024:Ligands; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019718:Receptors, CXCR4