Epimerization in peptide thioester condensation

Kenta Teruya, Takeyuki Tanaka, Toru Kawakami, Kenichi Akaji, Saburo Aimoto

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)669-677
Number of pages9
JournalJournal of Peptide Science
Issue number11
Publication statusPublished - 2012 Nov
Externally publishedYes


  • Epimerization
  • Peptide condensation
  • Peptide thioester

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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