Synthesis of O-Phosphotyrosine-Containing Peptides. II. Solution-Phase Synthesis of Asn-Glu-PTyr-Thr-Ala Through Methyl Phosphate Protection

Abstract

The PTyr (O-phosphotyrosine) pentapeptide H-Asn-Glu-Tyr(PO3H2)-Thr-Ala-OH.HO2CCF3, which is a naturally occurring sequence from the autophosphorylated Rous sarcoma virus pp60V-SrC, was prepared in high yield by the use of Boc-Tyr(PO3Me2)-OH in the Boc mode of solution-phase peptide synthesis. The protected pentapeptide, Z-Asn-Glu(OBzl)-Tyr(PO3Me2)-Thr(Bzl)-Ala-OBzl, was deprotected by a two-stage procedure which involved initial palladium-catalysed hydrogenolysis followed by the removal of the phosphate methyl groups by the use of one of the following treatments: (A) 10% bromotrimethylsilane/acetonitrile, (B) 1 M bromotrimethylsilane/thioanisole in trifluoroacetic acid, or (C) trifluoromethanesulfonic acid/trifluoroacetic acid/dimethyl sulfide/m-cresol.