A chemical genetic method for generating bivalent inhibitors of protein kinases

A new chemical genetic method to generate bivalent ligands of protein kinase inhibitors, composed of two components, first a synthetic, small molecule that targets the ATP-binding cleft and second a peptidic ligand that enhances selectivity between kinases is reported. The utility of new methodology is demonstrated through the generation of a panel of protein-small molecule conjugates that simultaneously target the SH1 and SH3 domains of the closely related tyrosine kinases Src and Abl.