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

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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.


This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Medicinal Chemistry, volume 49, issue 11, 2006 following peer review. The definitive publisher-authenticated version is available online at DOI: 10.1021/jm060334k.


American Chemical Society