Incorporation of phosphotyrosyl mimetic 4-(phosphonodifluoromethyl)phenylalanine (F2Pmp) into signal transduction-directed peptides.

Phosphotyrosyl (pTyr)-containing sequences in proteins serve important roles in cellular signal transduction. Often, synthetic pTyr-containing peptides based on cognate sequences surrounding these pTyr residues can exhibit pharmacologically useful properties of full phosphoproteins. However, such pTyr-containing peptides have limited use in whole-cell systems resulting from lability of the phosphate ester bond to protein-tyrosine phosphatases (PTPs). For this reason, a number of phosphatase-stable pTyr mimetics have been developed that retain certain of the chemical and pharmacological properties of pTyr itself. Among these, difluoro-phosphonomethyl phenylalanine (F2Pmp) has shown widespread utility in a variety of signal transduction settings, particularly those involving PTPs. This chapter provides practical techniques for the synthesis of a range of F2Pmp-containing peptides.