Liu C.-F,
Tam JP.
* Vanderbilt University, Nashville, USA
Chemical Ligation Approach To Form a Peptide Bond between Unprotected Peptide Segments:
Concept and Model Study.
J. Am. Chem. Soc. 1994;
116: 4149-4153
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 Cα-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.
