p56(lck) SH2 domain binding motifs from bead binding screening of peptide libraries containing phosphotyrosine surrogates

Abstract

Phosphorylation reactions are key mediators in a variety of biochemical signal processes. Research into the selective inhibition of protein tyrosine kinases to generate anticancer agents has made O-phosphotyrosyl analogues important pharmacological tools. The simple procedures reported here involving the formation of iterative peptide libraries together with the development of a selective and sensitive bead-binding assay have made it possible to rapidly screen peptides incorporating O-phosphotyrosyl surrogates (including O-phospho-2,3,5,6-tetrafluorotyrosine, 4-(phosphono)hydroxymethyl- phenylalanine and 4-(phosphono)fluoromethyl-phenylalanine) for their potential to inhibit the protein tyrosine kinase p56(lck). These procedures can be easily adapted to combinatorial peptide libraries.