Synthesis of Casein-Related Peptides and Phosphopeptides. VI. The Efficient Global 'Phosphite-Triester' Phosphorylation of Multiple-Serine-Containing Peptides by Using Dibenzyl N,N-Diethylphosphoramidite

Abstract

The peptide Ac-Ser(P)- NHMe and the multiple-Ser(P)-containing peptides Ac-Ser(P)-Ser(P)- NHMe and Ac-Ser(P)-Ser(P)-Ser(P)- NHMe were prepared in good yield by a global phosphorylation approach which employed benzyl phosphate protection. The three serine-containing peptides were phosphorylated by the use of dibenzyl N,N-diethylphosphoramidite/1H-tetrazole followed by in situ oxidation of the resultant dibenzyl phosphite-triesters with m- chloroperoxybenzoic acid. The protected Ser(PO₃Bzl₂)-containing peptides were purified by C₁₈ reverse-phase silica flash column chromatography and the benzyl phosphate groups were cleaved from the protected Ser(PO₃Bzl₂) peptides by palladium- catalysed hydrogenolysis.