Synthesis and Structure−Activity Relationships of Linear and Conformationally Constrained Peptide Analogues of CIYKYY as Src Tyrosine Kinase Inhibitors
- 29 April 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 49 (11) , 3395-3401
- https://doi.org/10.1021/jm060334k
Abstract
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 μM) and conformationally constrained peptide 31 (IC50 = 0.28 μM) exhibited 750- and 1400-fold higher inhibitory activities, respectively, versus that of 1 (IC50 = 400 μM). Compound 2 exhibited a partial competitive inhibition pattern against ATP.Keywords
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