Epimerization in peptide thioester condensation
Article first published online: 13 SEP 2012
Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 18, Issue 11, pages 669–677, November 2012
How to Cite
Teruya, K., Tanaka, T., Kawakami, T., Akaji, K. and Aimoto, S. (2012), Epimerization in peptide thioester condensation. J. Peptide Sci., 18: 669–677. doi: 10.1002/psc.2452
- Issue published online: 18 OCT 2012
- Article first published online: 13 SEP 2012
- Manuscript Accepted: 17 AUG 2012
- Manuscript Revised: 6 AUG 2012
- Manuscript Received: 2 MAY 2012
- peptide thioester;
- peptide condensation
Peptide segment couplings are now widely utilized in protein chemical synthesis. One of the key structures for the strategy is the peptide thioester. Peptide thioester condensation, in which a C-terminal peptide thioester is selectively activated by silver ions then condensed with an amino component, is a powerful tool. But the amino acid adjacent to the thioester is at risk of epimerization. During the preparation of peptide thioesters by the Boc solid-phase method, no substantial epimerization of the C-terminal amino acid was detected. Epimerization was, however, observed during a thioester–thiol exchange reaction and segment condensation in DMSO in the presence of a base. In contrast, thioester–thiol exchange reactions in aqueous solutions gave no epimerization. The epimerization during segment condensation was significantly suppressed with a less polar solvent that is applicable to segments in thioester peptide condensation. These results were applied to a longer peptide thioester condensation. The epimer content of the coupling product of 89 residues was reduced from 27% to 6% in a condensation between segments of 45 and 44 residues for the thioester and the amino component, respectively. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.