Potent inhibition of protein-tyrosine phosphatese-1B using the phosphotyrosyl mimetic fluoro-O-malonyl tyrosine (FOMT)

To enhance PTP binding interactions, both inside and outside the pTyr binding pocket, a thioether-cyclized peptide has been designed based on the EGF receptor autophosphorylation sequence (EGFR988–993) “Asp-Ala-Asp-Glu-pTyr-Leu”, in which the pTyr residue has been replaced by the nonphosphorus-containing pTyr mimetic fluoro-O-malonyltyrosine (FOMT, 2). The resulting peptide 4 exhibits a Ki value of 170 nM, making it one of the most potent inhibitors of PTP1B yet reported.