Chemical Ligation of Unprotected Peptide Segments

Key words

chemical ligation - peptide bond - acyl transfer - pentadecapeptide

Significance

The authors describe an approach for the chemical ligation of peptide segments by thiazolidine ring formation. The method does not require protecting groups or the activation of the C^α-carboxyl group in the conventional sense. The main feature of the approach is that it overcomes the entropy barrier to intermolecular reaction ­between two large molecules. Furthermore, this method was successfully used in the synthesis of a pentadecapeptide.

Comment

This chemical ligation approach of unprotected segments proceeds through three steps: (1) introduction of an aldehyde group at a C-terminal site, (2) ring formation, and (3) O-to-N acyl transfer. These steps eliminate the need for protecting groups and permit the ligation to proceed in aqueous solution.