Synthesis of protected peptide fragments and release from a solid support under neutral conditions

Abstract

A linker has been developed for use in solid-phase peptide synthesis which allows a protected peptide to be cleaved from the resin under neutral conditions (nBu 3P, DMF, imidazole buffer pH 7) whilst retaining tBuO-, Boc- and Fmoc-protecting groups. The linker comprises a 2-azidomethyl-4-hydroxy-6,N-dimethylbenzamide moiety, which is coupled to polystyrene resin as a phenol ether and to the peptide via a N-hydroxymethyl group. The protected peptide fragments so produced may be useful, for example, in subsequent fragment condensations using the Fmoc-chemistry.