A novel phosphotyrosine mimetic 4′-carboxymethyloxy-3′-phosphonophenylalanine (cpp): exploitation in the design of nonpeptide inhibitors of pp60 Src SH2 domain

Abstract

The novel phosphotyrosine (pTyr) mimetic 4′-carboxymethyloxy-3′-phosphonophenylalanine (Cpp) has been designed and incorporated into a series of nonpeptide inhibitors of the SH2 domain of pp60 c-Src (Src) tyrosine kinase. A 2.2 Å X-ray crystal structure of 1a bound to a mutant form of Lck SH2 domain provides insight regarding the structure–activity relationships and supports the design concept of this new pTyr mimetic.