鲑鱼降钙素(sCT)类似物在水溶液中的化学稳定性

CHEMICAL STABILITY OF SALMON CALCITONIN (sCT) ANALOGUES IN AQUEOUS SOLUTION

用反相高效液相色谱和快原子轰击质谱方法（ＦＡＢＭＳ），研究了３个鲑鱼降钙素（ｓＣＴ）类似物［Ｖａｌ１，Ａｌａ７］ｓＣＴ，［Ｖａｌ１，Ａｌａ７，Ａｌａ３０］ｓＣＴ和［ＤＡｌａ３０］ｓＣＴ在不同ｐＨ和温度下水溶液中的化学稳定性，并对ｓＣＴ及其类似物在ｐＨ９０水溶液中的部分降解产物通过ＦＡＢＭＳ进行了确证。结果表明，ｓＣＴ及其３个类似物在水溶液中的化学降解对ｐＨ依赖性较大，在碱性条件下易降解。提示不含二硫键的直链肽类似物［Ｖａｌ１，Ａｌａ７］ｓＣＴ和［Ｖａｌ１，Ａｌａ７，Ａｌａ３０］ｓＣＴ的化学稳定性比ｓＣＴ高，而［ＤＡｌａ３０］ｓＣＴ的化学稳定性则相对降低。

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 [Val1,Ala7]sCT, [Val1,Ala7,Ala30]sCT and [DAla30]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 [Val1,Ala7]sCT and [Val1,Ala7,Ala30]sCT showed higher chemical stability than sCT while [DAla30]sCT showed lower chemical stability than the native sCT.