Synthesis and Structure-Activity Relationships of Linear and Conformationally Constrained Peptide Analogs of CIYKYY as Src Tyrosine Kinase Inhibitors

摘要

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