Structure-based design of a novel series of nonpeptide ligands that bind to the pp60src SH2 domain

It has been established that phosphotyrosine-containing peptides bind to the SH2 domain of pp60c-src (Src), a nonreceptor tyrosine kinase, with micromolar affinity. Researchers have been able to design a de novo series of small molecule ligands that bind with affinity comparable to the parent phosphopeptide. The unusual binding at the P-site may be used as a basis for designing new phosphate mimetics that are more conducive to cell penetration and higher levels of bioavailability.