Structure-based design of novel, dipeptide ligands targeting the pp60Src SH2 domain

Abstract Based on the X-ray structures of the pp60 Src (Src) SH2 domain complexed with two high affinity phosphopeptide ligands (Glu-Pro-Gln-pTyr-Glu-Glu-Ile-Pro-Ile-Tyr-Leu, and Ac-pTyr-Glu- D -Hcy-NH 2 ; Hcy = homocyclohexylalanine), we report herein the design and structure-activity relationships of a series of novel dipeptide ligands targeting the Src SH2 domain.