Highly selective cleavage of pyroglutamyl-peptide bond in concentrated hydrochloric acid

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 degree 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.