Synthesis of substance P partial sequential peptides on a photolytically removable 4-aminomethyl-3-nitrobenzoylaminomethyl polystyrene support

Abstract

Sequential peptides corresponding to substance P (6–11) were synthesised on a photocleavable 4-aminomethyl-3-nitrobenzoylaminomethyl polystyrene resin. This photoremovable polymeric support, useful for the synthesis of C-terminal peptide amides, was prepared from 4-bromomethyl-3-nitrobenzoylaminomethyl polystyrene by treatment with potassium phthalimide followed by hydrazinolysis. Amino acid residues were incorporated onto this support following the standard solid-phase methodology of peptide synthesis. The protected peptide amides were cleaved from the resin by photolysis with light of wavelength 350 nm. The resin was used for the synthesis of peptides including the partial sequence corresponding to substance P (9-11) which was further subjected to stepwise synthesis to prepare substance P (6-11) in an overall yield of 88%. This approach combines the advantages of the photochemical deprotection of the 4-aminomethyl-3-nitro carboxyl protecting group, the polymer-supported peptide synthesis and the polymer-analogous functionalisation procedure to obtain the C-terminal peptide amide under mild conditions.