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ID: ALA1131573

Journal: J Med Chem

Title: Potent dipeptide inhibitors of the pp60c-src SH2 domain.

Authors: Pacofsky GJ, Lackey K, Alligood KJ, Berman J, Charifson PS, Crosby RM, Dorsey GF, Feldman PL, Gilmer TM, Hummel CW, Jordan SR, Mohr C, Shewchuk LM, Sternbach DD, Rodriguez M.

Abstract: The design, synthesis, and evaluation of dipeptide analogues as ligands for the pp60c-src SH2 domain are described. The critical binding interactions between Ac-Tyr-Glu-N(n-C5H11)2 (2) and the protein are established and form the basis for our structure-based drug design efforts. The effects of changes in both the C-terminal (11-27) and N-terminal (51-69) portions of the dipeptide are explored. Analogues with reduced overall charge (92-95) are also investigated. We demonstrate the feasibility of pairing structurally diverse subunits in a modest dipeptide framework with the goal of increasing the druglike attributes without sacrificing binding affinity.

CiteXplore: 9599239

DOI: 10.1021/jm970853a