Novel Facilitation of Peptide Synthesis

Abstract

THE “solid phase” method of synthesizing peptides¹, in which the carbon-terminal residue is first esterified to a hydroxymethylpolystyrene resin, has been used successfully for the rapid synthesis in high yield of peptides which can be purified after removal from the resin². If such a procedure, which omits the purification of intermediates, is to yield a homogeneous product without further purification, every stage must proceed to completion. For example, if 0.5 per cent of the amino-groups remain unacylated after each coupling, then after one hundred stages the product will contain only 61 per cent of the required peptide, the remainder being peptides with closely similar but defective sequences. It is a serious disadvantage of the solid phase method that one of the reactants is polymeric, making it difficult to force reactions to completion.