Novel synthesis through repeated S-cyanocysteine mediated segment condensations

Abstract

Segment condensation of unprotected peptides is a very interesting approach for total synthesis of proteins [1–4] and a combinatorial synthesis. It is wellknown that the cleavage reaction of an S -cyanocysteinyl peptide generate an amino-terminal peptide and a carboxyl-terminal fragment blocked by a 2-iminothiazolidine[5,6]. We speculated that the intermolecular attack of an α-amino group on the activated carbonyl carbon atom would also occur and the binding of a S -cyanocysteinyl peptide with an α -amino group of an N-terminal free peptide would be possible. We demonstrate here that an S-cyanocysteine-mediated α-carbon activation is useful for combining two peptide segments with peptide bonding, and also propose a strategy for the repeated segment condensation using the S-cyanocysteinyl peptide as a building block.