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【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。
【Objective】 To establish a high-throughput screening model targeting Mycobacterium tuberculosis protein kinase B and use this model to screen compounds. 【Method】 Mycobacterium tuberculosis protein kinase B was cloned and expressed, and a high-throughput screening model of PknB inhibitor was established and optimized by using it as a target enzyme. The compound was screened by the model and the positive compounds screened for antibacterial activity And inhibition of enzyme activity evaluation. 【Result】 A total of 18 000 compounds were screened by this model. Eight of the compounds with inhibitory activity were obtained. Three of them showed good inhibitory activity against Mycobacterium tuberculosis, Mycobacterium maritima and Mycobacterium smegmatis Antibacterial activity. 【Conclusion】 The established high-throughput screening model of anti-TB drugs targeting PknB has the advantages of high sensitivity and stability, and can be successfully used in the screening of compounds. Three positive compounds which have good activity in inhibiting aprotinin and antimicrobial activity were selected and screened for further study.