Fmoc-based solid-phase peptide synthesis using dpr(phoc) linker. Synthesis of a C-terminal proline peptide

Abstract Cyclic acylurea readily formed from Dpr(Phoc) linker was shown to provide linkage that is fully compatible with standard Fmoc-based solid-phase peptide synthesis protocols. The utility of this linkage was checked during Tyr-Asp-Pro-Ala-(Pro) 6 -OH synthesis which is very prone to diketopiperazine formation at the dipeptide stage. This side-reaction was avoided by maintaining the Dpr(Phoc) linker until the tripeptide stage, while piperidine had to be temporary replaced with morpholine as reagent for Fmoc group removal.