Epimerization in peptide thioester condensation

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

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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
Volume18
Issue number11
DOIs
Publication statusPublished - 2012 Nov
Externally publishedYes

Keywords

  • 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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