Yang B, Cai Y, Han Z, Wu L, Ding Z, Zhang Q, Yang S
Beijing Institute of Pharmacology & Toxicology, National Center of Biomedical Analysis, Beijing 100850.
Yao Xue Xue Bao. 1998 Aug;33(8):610-5.
Calcitonin is a peptide hormone with 32 amino acids. Natural calcitonins are presumably quite unstable in solution and numerous analogues of calcitonin had been synthesized to improve the stability. In the present paper, we report the investigation of the chemical stability of salmon calcitonin (sCT) analogues [Val1, Ala7]sCT, [Val1, Ala7, Ala30]sCT and [D-Ala30]sCT in aqueous solutions by reversed phase high-performance liquid chromatography (RP-HPLC) and fast atom bombardment mass spectrometry (FAB-MS) methods. The degradation patterns of the sCT analogues showed a marked dependence on pH and temperature. Most of the degradation products in pH 9.0 solution of sCT and its analogues were identified by FAB-MS analysis. Results showed that the sCT analogues are more stable at pH 3.3 and pH 3.7 than at pH 6.0 and pH 9.0. Analogues without disulfide bridge [Val1, Ala7]sCT and [Val1, Ala7, Ala30]sCT showed higher chemical stability than sCT while [D-Ala30]sCT showed lower chemical stability than the native sCT.
降钙素是一种含有32个氨基酸的肽类激素。天然降钙素在溶液中可能相当不稳定,因此人们合成了许多降钙素类似物以提高其稳定性。在本文中,我们报告了通过反相高效液相色谱法(RP-HPLC)和快原子轰击质谱法(FAB-MS)对鲑鱼降钙素(sCT)类似物[Val1, Ala7]sCT、[Val1, Ala7, Ala30]sCT和[D-Ala30]sCT在水溶液中的化学稳定性进行的研究。sCT类似物的降解模式显示出对pH值和温度的显著依赖性。通过FAB-MS分析鉴定了sCT及其类似物在pH 9.0溶液中的大多数降解产物。结果表明,sCT类似物在pH 3.3和pH 3.7时比在pH 6.0和pH 9.0时更稳定。不含二硫键的类似物[Val1, Ala7]sCT和[Val1, Ala7, Ala30]sCT显示出比sCT更高的化学稳定性,而[D-Ala30]sCT显示出比天然sCT更低的化学稳定性。