天然产物研究与开发 ›› 2016, Vol. 28 ›› Issue (6): 916-921.doi: 10.16333/j.1001-6880.2016.6.017

• 开发研究 • 上一篇    下一篇

微生物来源的α-葡萄糖苷酶抑制剂高通量筛选模型的建立和初步应用

于彩云1,赵莉莉2,张晶晶1,魏涛1*   

  1. 1 北京联合大学 生物活性物质与功能食品北京市重点实验室,北京 100191;2 中国医学科学院 北京协和医学院医药生物技术研究所,北京 100050
  • 出版日期:2016-06-30 发布日期:2017-01-17

Development and Preliminary Application of High Throughput Screening Model of α-Glycosidase Inhibitor from Microorganism

YU Cai-yun1,ZHAO Li-li2,ZHANG Jing-jing1,WEI Tao1*   

  1. 1 Beijing Key Laboratory of Bioactive Substances and Function Food,Beijing Union University,Beijing 100191,China; 2 Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050,China
  • Online:2016-06-30 Published:2017-01-17

摘要: 本研究用昆明种小鼠十二指肠上段提取的α-葡萄糖苷酶,以4-硝基苯-α-D-吡喃葡萄糖苷为反应底物,建立α-葡萄糖苷酶抑制剂高通量筛选模型。用该模型对1276株放线菌和132株细菌等共计2224个发酵液粗提物样品进行筛选。初筛得到抑制率超过50%的阳性样品23个,初筛阳性率为1.03%。将阳性菌株再次进行发酵提取,得到新发酵液的阳性样品数为17,复筛阳性率为0.74%。其中细菌3株,放线菌13株。3个阳性样品经α-葡萄糖苷酶验证后的抑制率均在75%以上。本研究建立的α-糖苷酶抑制剂高通量筛选模型具有很强的实用价值,可用于新型糖尿病药物的开发。

关键词: &alpha, -葡萄糖苷酶抑制剂, 高通量筛选模型, 微生物发酵液粗提物, 糖尿病

Abstract: The α-glycosidase was extracted from the upper duodenum of Kunming mice.4-Nitrophenyl-α-D-glucopyranoside was used as substrate to establish a high throughput drug screening model of α-glycosidase inhibitor.A total of 2224 microbial fermentation extracts,including 1276 strains of actinomycetes and 132 strains of bacteria,were screened.23 positive samples were obtained,with a 1.03% positive rate at the first screening.The 23 strains were fermented and extracted for a second time,17 positive samples were obtained,with 3 bacterium and 13 actinomycetes.The positive rate was 0.74%.3 Positive samples were verified by α-glycosidase to have inhibitory effects higher than 75%.In conclusion,the developed α-glycosidase inhibitor high-throughput screening model had high practical value for developing new hypoglycemic drugs.

Key words: Alpha-glycosidase inhibitor, high-throughput screening model, microbial fermentation extract, Diabetes Mellitus

中图分类号: 

Q815 R977.1+5