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,Ai Esaka,Shinya Oishi,Nami Ohashi,Kyoko Itotani,Barry J. Evans,Stephen C. Peiper,Nobutaka Fujii,Hirokazu Tamamura
Organic & Biomolecular Chemistry Pub Date : 07/20/2009 00:00:00 , DOI:
10.1039/B908286GAbstract
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.
