天然产物研究与开发 ›› 2015, Vol. 27 ›› Issue (7): 1140-1145.doi: 10.16333/j.1001-6880.2015.07.003

• 研究论文 • 上一篇    下一篇

谷胱甘肽的合成与其活性初步评价

代涛,李松涛,赵红玲,王小青,王良友*   

  1. 河北省中药研究与开发重点实验室 承德医学院中药研究所,承德 067000
  • 出版日期:2015-07-20 发布日期:2015-07-23

Synthesis of Glutathione and Preliminary Evaluation of Their Biological Activities

DAI Tao, LI Song-tao, ZHAO Hong-ling, WANG Xiao-qing, WANG Liang-you*   

  1. The Key Laboratory of Chinese Medicine Research and Development of Hebei Province,Institute of Chinese Materia Medica,Chengde Medical College,Chengde 067000,China
  • Online:2015-07-20 Published:2015-07-23

摘要: 先采用Fmoc固相多肽合成法,以2-Chlorotrityl chloride(2-CTC)树脂做载体,DIC/HOBt做缩合剂,逐步缩合得到全保护谷胱甘肽树脂,以TFA/EDT/m-Cresol为裂解液脱除保护基团,粗肽经半制备反相高效液相色谱法纯化得α-GSH、γ-GSH纯品,后将所得γ-GSH纯品分别采用空气,双氧水,碘氧化得GSSG,经纯化得GSSG纯品,合成的α-GSH、γ-GSH纯品纯度达99%,GSSG纯度达98%,利用标准品,经外标法计算总收率分别为60%、64%、57%。并观察三者对CCl4诱导的小鼠急性肝损伤的治疗效果结果显示都能显著降低ALT与AST的活性,且与注射用γ-GSH没有显著性差异,可以为工业化生产提供借鉴。

关键词: 谷胱甘肽, 固相多肽合成, 二硫键形成, 生物活性

Abstract: In this study,α-GSH and γ-GSH were synthesized by Fmoc solid phase peptide synthesis method,using 2-chlorotrityl chloride (2-CTC) resin as solid carrier and DIC/HOBt as condensing agents.The protected peptide was obtained by cleavage with TFA/EDT/m-Cresol.The crude GSSG peptide was then formed by air,H2O2 or I2 oxidation of γ-GSH separately.After semi-preparative RP-HPLC purification,three pure peptides were obtained.The purities of α-GSH,γ-GSH,GSSG pure peptide were 99%,99%,98%,and the total yields were 60%,64%,57%,respectively.Finally,their hepatoprotective effect on CCl4-induced acute liver injury in mice was observed.The result showed that three synthetic pure peptides can significantly decrease ALT and AST activities in mice serum,and there were no significant differences with γ-GSH for injection,which may provide reference for industrial production.

Key words: glutathione, Fmoc solid phase peptide synthesis, disulfide bond formation, biological activity

中图分类号: 

R914.5