Synthesis of Casein-Related Peptides and Phosphopeptides. XIII. Solid Phase Synthesis of GLu-Ser(P)-Leu Through Global Phosphorylation of a Resin-Bound Seryl-Containing Peptide

Abstract

The solid phase synthesis of CF₃CO₂H.H-Glu-Ser(P)-Leu-OH by the 'global' 'phosphite-triester' phosphorylation of a polystyrene resin-bound seryl -containing peptide by using either dibenzyl or di -t-butyl N,N- diethylphosphoramidite is described. The seryl -containing peptide resin was prepared by successive dicyclohexylcarbodiimide/1H-benzotriazol-1-ol couplings of Fmoc -Ser(Bu^t)-OH and Z- Glu ( OBzl )-OH to Boc-Leu-resin (polystyrene) followed by cleavage of the seryl t-butyl ether group with 90% CF₃CO₂H/CH₂Cl₂. The seryl hydroxy group was phosphorylated by the use of either dibenzyl or di -t-butyl N,N-diethylphosphoramidite/1H- tetrazole followed by m-chloroperoxybenzoic acid oxidation of the resultant phosphite triester. With benzyl phosphate protection, the protected Ser(PO₃Bzl₂)-containing peptide resin was deprotected by high-pressure hydrogenation with palladium acetate. In the case of t-butyl phosphate protection, the t-butyl groups were first cleaved by treatment with 10% CF₃CO₂H/CH₂Cl₂ and the Ser(PO₃H₂) tripeptide was then cleaved from the resin support by high-pressure hydrogenation in the presence of palladium acetate.