SYNTHESIS OF A PHOSPHOTYROSINE-CONTAINING PEPTIDE FRAGMENT OF THE REGULATORY DOMAIN OF PP60(C-SRC)

t-Boc-Tyr(PO(3)Me(2))-OH (4) was ulitized in the synthesis of PheThrSerThrGluProGlnTyr(PO3H2)-GlnProGlyGluAsnLeu (1), a phosphotyrosine-containing peptide fragment of the regulatory domain of pp60(c-src). The protected amino acid 4 was employed during the synthesis of PheThrSerThrGluProGlnTyr(PO(3)Me(2))GlnProGlyGluAsnLeu (5), during which problems involving incomplete incorporation of the Tyr(PO(3)Me(2)) residue, as well as partial demethylation of the dimethylphosphono group and dephoshhorylation during peptide synthesis, were encountered. In addition, an acid-catalyzed backbone rearrangement was encountered involving migration of the phenylalanine acyl group from the nitrogen to the hydroxyl group of the adjacent threonine residue during the deprotection of the phosphate group of 5 with a mixture of trifluoromethanesulfonic acid, trifluoroacetic acid, dimethyl sulfide, and m-cresol (10:50:30:10).