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

Authors

Anil Kumar, University of Rhode Island
Guofeng Ye, University of Rhode Island
Yuehao Wang, University of Rhode Island
Xiaofeng Lin, University of Rhode Island
Gongqin Sun, University of Rhode Island
Keykavous Parang, University of Rhode Island

Document Type

Article

Date of Original Version

6-1-2006

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. © 2006 American Chemical Society.

Publication Title, e.g., Journal

Journal of Medicinal Chemistry

Volume

49

Issue

11

Citation/Publisher Attribution

Kumar, Anil, Guofeng Ye, Yuehao Wang, Xiaofeng Lin, Gongqin Sun, and Keykavous Parang. "Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors." Journal of Medicinal Chemistry 49, 11 (2006): 3395-3401. doi: 10.1021/jm060334k.