Hydrolytic Cleavage of Pyroglutamyl-peptide Bond. III. A Highly Selective Cleavage in 70% methanesulfonic Acid

• Published in: Chemical & pharmaceutical bulletin Vol. 44; no. 11; pp. 2033 - 2036
• Main Authors: HASHIMOTO, Tadashi, OHKI, Kazuhiro, SAKURA, Naoki
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1996; Maruzen; Japan Science and Technology Agency
• Subjects: 70% methanesulfonic acid; Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; cleavage reaction; Dogs; Fundamental and applied biological sciences. Psychology; Hydrolysis; Indicators and Reagents; Mesylates - chemistry; Neuropeptides - chemistry; Peptides - chemistry; Peptides - isolation & purification; Proteins; pyroglutamyl-peptide; pyroglutamyl-peptide bond; Pyrrolidonecarboxylic Acid - chemistry; Hydrolysis; Peptides; Peptide bond; Pyroglutamic acid; Tripeptide; Methanesulfonic acid; Heptapeptide; Aqueous solution
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.44.2033

A method for highly selective cleavage of pGlu-peptide linkages in 70% methanesulfonic acid (MSA) is described. When pGlu-Ala-Phe-OH, pGlu-His-Pro-OH and dog neuromedin U-8 (d-NMU-8) (1-7)-OH (pGlu-Phe-Leu-Phe-Arg-Pro-Arg-OH) were hydrolyzed in 70% MSA at 60°C for 3 h or at 25°C for 3 d, the pGlu-peptide linkage was predominantly cleaved to give H-Ala-Phe-OH, H-His-Pro-OH and H-Phe-Leu-Phe-Arg-Pro-Arg-OH, in high yields. The results indicated that pGlu-peptide linkages are highly susceptible to 70% MSA, whereas the amide bond of the pyrrolidone moiety of the pGlu residue and other internal peptide bonds are extremely resistant.