Hashimoto T, Ohki K, Sakura N
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Chem Pharm Bull (Tokyo). 1995 Dec;43(12):2068-74. 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 degrees 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 degrees 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-operating reaction was greatly diminished at 4 degrees 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 bond appears to be a general one.
研究了一些生物活性肽中焦谷氨酰 - 肽键，即犬神经介素U - 8片段（pGlu - Phe - Leu - Phe - Arg - Pro - Arg - OH）、人 big胃泌素片段（pGlu - Leu - Gly - Pro - OH）和促甲状腺激素释放激素（TRH）片段（pGlu - His - Pro - OH、pGlu - His - OH）在温和条件下和/或60℃时对1 N盐酸的敏感性。发现pGlu - 肽的N端部分对酸水解极其不稳定，不仅产生pGlu残基吡咯烷酮部分的开环产物，还产生pGlu - 肽键的裂解产物。在60℃的1 N盐酸中水解这四种肽时，开环反应比裂解反应占优势。pGlu - 肽键的开环反应和裂解反应比内部肽键的裂解进行得更快。水解速率受反应温度影响，与裂解反应相比，在4℃时开环反应大大减弱。因此，与其他肽键相比，pGlu - 肽键对稀盐酸敏感的现象似乎是普遍存在的。
