以蛋白激酶B为靶点的新型抗结核药物高通量筛选模型的建立和应用

发布时间：2018-05-15 13:07

本文选题：蛋白激酶B + 药物筛选模型　；参考：《微生物学通报》2014年04期

【摘要】：【目的】建立以结核分枝杆菌蛋白激酶B为靶点的高通量筛选模型,并运用此模型进行化合物的筛选。【方法】克隆和表达结核分枝杆菌蛋白激酶B,并以其为靶酶建立并优化PknB抑制剂高通量筛选模型,利用该模型对化合物样品进行筛选,并对筛选到的阳性化合物进行抗菌和抑酶活性评价。【结果】利用该模型筛选了化合物样品18 000个,得到具有抑酶活性的阳性化合物8个,其中3个化合物具有较好的对结核分枝杆菌、海分枝杆菌、耻垢分枝杆菌的抑菌活性。【结论】建立的以PknB为靶点的抗结核药物高通量筛选模型具有灵敏度高、稳定性强等优点,可成功用于化合物的高效筛选。筛选得到3个在抑酶水平和抗菌方面均具有良好活性的阳性化合物样品,值得进一步研究。
[Abstract]:[objective] to establish a high-throughput screening model targeting Mycobacterium tuberculosis protein kinase B. This model was used to screen compounds. [methods] cloning and expression of protein kinase B of Mycobacterium tuberculosis was used to establish and optimize the high-throughput screening model of PknB inhibitor. The antibacterial and enzyme inhibitory activities of the selected positive compounds were evaluated. [results] using this model, 18,000 samples of compounds were screened, and 8 positive compounds with inhibitory activity were obtained. Three of the compounds had good antibacterial activity against Mycobacterium tuberculosis, Mycobacterium hirsurea and Mycobacterium smearicus. [conclusion] the model of high throughput screening of antituberculous drugs with PknB as target has high sensitivity. Because of its strong stability, it can be successfully used in the screening of compounds. Three positive compounds with good activity in enzyme inhibition and antimicrobial activity were obtained, which are worthy of further study.
【作者单位】：中国医学科学院北京协和医学院医药生物技术研究所;
【基金】：国家自然科学基金项目(No.30970038,81373452) 国家微生物资源平台项目(No.NIMR-2013-3)
【分类号】：R521

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