Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as src tyrosine kinase inhibitors

摘要

A series of peptide analogues of Ac-CIYKYY (1) were synthesized by functional group modifications in peptide side chains or by introducing conformational constraints, to improve the inhibitory potency against active Src kinase. Ac-CIYKF(4-NO2) Y ( 2, IC50) 0.53 mu M) and conformationally constrained peptide 31 (IC50) 0.28 mu M) exhibited 750- and 1400-fold higher inhibitory activities, respectively, versus that of 1 (IC50) 400 mu M). Compound 2 exhibited a partial competitive inhibition pattern against ATP.