An improved soluble polynorbornene support for peptide synthesis

Abstract

Soluble polymers that can be readily isolated via precipitation and possess multiple amino acid attachment sites are highly attractive for peptide synthesis. Polyethylene glycol supports that solubilize the growing peptide chain and can be readily isolated have been widely used for peptide synthesis. However, a stoichiometric amount of the PEG support is required because each PEG support typically has a single attachment site for peptide synthesis. Reported herein is the development of a polynorbornene support containing multiple attachment sites as well as alkyl and oligoether solubilizing/spacer groups. The attachment site is connected to the polymer backbone through a solubilizing oligoether linker. The support was developed after evaluating the effect of the linker and attachment site-spacing on peptide synthesis using suitably designed polynorbornene supports. The high solubility of the support minimizes the equivalents of reagents used for peptide synthesis. The support has been used to synthesize the natural product Leu⁵-enkephalin in 52% overall yield using only 1.2 equivalents of coupling reagents, which is comparable or superior to reported procedures using a large excess of reagents.