HIGHLY SELECTIVE CLEAVAGE OF PYROGLUTAMYL-PEPTIDE BOND IN CONCENTRATED HYDROCHLORIC ACID

• Published in: Chemical & pharmaceutical bulletin Vol. 44; no. 4; pp. 877 - 879
• Main Authors: HASHIMOTO, Tadashi, SAITO, Susumu, OHKI, Kazuhiro, SAKURA, Naoki
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 1996; Pharmaceutical Soc Japan; Maruzen; Japan Science and Technology Agency
• Subjects: Amino Acid Sequence; Animals; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; cleavage reaction; Dogs; Exact sciences and technology; Hydrochloric Acid; Hydrolysis; Kinetics; Life Sciences & Biomedicine; Molecular Sequence Data; Organic chemistry; Peptides; Peptides - chemistry; Pharmacology & Pharmacy; Physical Sciences; Preparations and properties; pyroglutamyl-peptide; pyroglutamyl-peptide bond; Pyrrolidonecarboxylic Acid - chemistry; Science & Technology; pyroglutamyl-peptide; pyroglutamyl-peptide bond; cleavage reaction; hydrochloric acid; hydrolysis; Hydrochloric acid; Hydrolysis; Peptides; Tetrapeptide; Pyroglutamic acid; Peptide synthesis; Selectivity; Heptapeptide; Chemical synthesis; N terminal aminoacid; Scission; Concentrated solution
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.44.877

Highly selective cleavage reaction of pGlu-peptide bond is described. Two model peptides, pGlu-X-Ala-Phe-OH (X=Ile and Ser), and dog neuromedin U-8 (d-NMU-8) (1-7)-OH (pGlu-Phe-Leu-Phe-Arg-Pro-Arg-OH) were hydrolyzed in concentrated HCl at 0°C for from 6 days to 6 weeks to give the predominant cleavage products of pGlu-X linkage of pGlu-X-Ala-Phe-OH and the pGlu-Phe linkage of d-NMU-8 (1-7)-OH, respectively. The ring-opening reaction of the pyrrolidone moiety of the pGlu residue occurred to a considerably lesser extent.