title: Epimerization in peptide thioester condensation.
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.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan. teruya@koto.kpu-m.ac.jp
authors.forename: Kenta
authors.initials: K
authors.lastname: Teruya
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Toru
authors.initials: T
authors.lastname: Kawakami
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
authors.forename: Saburo
authors.initials: S
authors.lastname: Aimoto
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000235:genetics; D011789:Quantum Theory; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D004952:Esters; D010455:Peptides; D013438:Sulfhydryl Compounds