Hydrolytic cleavage of pyroglutamyl-peptide bond. I. The susceptibility of pyroglutamyl-peptide bond to dilute hydrochloric acid

Article abstract of DOI:10.1248/cpb.43.2068

The susceptibility of the pyroglutamyl-peptide bond in some biologically active peptides, dog neuromedin U-8 fragment (pGlu-Phe-Leu-Phe-Arg-Pro-Arg- OH), human big gastrin fragment (pGlu-Leu-Gly-Pro-OH) and thyrotropin releasing hormone (TRH) fragments (pGlu-His-Pro-OH, pGlu-His-OH), to 1 N HCl under mild conditions and/or at 60°C was studied. It was found that the N- terminal portion of pGlu-peptides is extremely labile to acid hydrolysis, giving not only the ring-opened product of the pyrrolidone moiety of the pGlu residue, but also the cleavage product of the pGlu-peptide linkage. The ring- opening reaction predominated over the cleavage reaction in hydrolysis of the four peptides in 1 N HCl at 60°C. The ring-opening reaction and the cleavage reaction of pGlu-peptide linkage proceeded faster than the cleavage of internal peptide bonds. The rate of hydrolysis was affected by the reaction temperature, and the ring-opening reaction was greatly diminished at 4°C in comparison with the cleavage reaction. Thus, the phenomenon that the pGlu- peptide bond is susceptible to dilute HCl as compared to the other peptide bonds appears to be a general one.

Full text of DOI:10.1248/cpb.43.2068

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service