1. Incorporation of phosphotyrosyl mimetic 4-(phosphonodifluoromethyl)phenylalanine (F2Pmp) into signal transduction-directed peptides
Zhu-Jun Yao, Kyeong Lee, Terrence R Burke Jr Methods Mol Biol. 2005;298:91-103. doi: 10.1385/1-59259-877-3:091.
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.
2. An efficient synthesis of a 4'-phosphonodifluoromethyl-3'-formyl-phenylalanine containing SRC SH2 ligand
W C Shakespeare, R S Bohacek, S S Narula, M D Azimioara, R W Yuan, D C Dalgarno, L Madden, M C Botfield, D A Holt Bioorg Med Chem Lett. 1999 Nov 1;9(21):3109-12. doi: 10.1016/s0960-894x(99)00545-4.
A CuBr-mediated, regioselective cross-coupling between methyl 2,5-diiodobenzoate (4) and [(diethoxyphosphinyl)difluoromethyl]zinc bromide is reported. Palladium-catalyzed incorporation of an amino acid side chain, followed by subsequent modifications resulted in the rapid construction of 2. Compound 2 was designed to engage Cys188 of the Src SH2 domain, however, this was not observed spectroscopically.
