Synthesis of Casein Related Peptides and Phosphopeptides. XIV. Solid Phase Synthesis of Glu-Ser(P)-Leu Through the Use of Protected Boc-Ser(PO₃R₂)-OH Derivatives

Abstract

A solid phase method is described for the synthesis of O- phosphoseryl-containing peptides by the use of polystyrene resin (Merrifield) as the peptide support and protected Boc-Ser(PO₃R₂)-OH derivatives for the incorporation of the phosphorylated seryl residue. The viability of this solid phase approach was demonstrated by the synthesis of HBr.H-Glu-Ser (PO₃Et₂)-Leu-OH in high yield by the use of Bo -Ser(PO₃Et₂)-OH in peptide synthesis and subsequent use of HBr/CF₃CO₂H for cleavage of the Ser(PO₃Et₂)-containing tripeptide from the resin support. Similarly, the dipeptide, CF₃CO₂H.H-Ser(P)- Leu -OH, was prepared in high yield by using Boc -Ser(PO₃Bu^t₂)-OH in peptide synthesis followed by the one-step deprotection of the Ser(PO₃Bu^t₂)- dipeptide resin by treatment with HBr/CF₃CO₂H (90 min).

Alternatively, the O-phosphoseryl tripeptide , CF₃CO₂H.H-Glu-Ser(P)- Leu -OH was prepared by using either Ppoc -Ser(PO₃Bzl₂)-OH or Boc-Ser(PO₃Ph₂)-OH in peptide synthesis. The one-step deprotection of the Ser(PO₃Bzl₂)-containing tripeptide and cleavage of the peptide from the resin support was effected by high-pressure hydrogenolysis (palladium acetate). In the case of phenyl phosphate protection, the Ser(PO₃Ph₂)-containing peptide was cleaved from the resin support by high-pressure hydrogenolysis (palladium acetate) followed by cleavage of the phenyl phosphate groups by platinum-mediated hydrogenolysis (1.0 equiv. PtO₂/phenyl group) in 50% CF₃CO₂H/AcOH.