抗革兰阴性菌靶向筛选平台的建立
发布时间：2018-11-21 07:39
【摘要】：目的建立靶向筛选抗革兰阴性菌新药的综合模型体系。方法以大肠埃希菌DH5α菌株作为革兰阴性菌的模式菌,利用反义RNA沉默技术特异性降低靶基因的表达水平,构建系列反义RNA低表达菌株,并基于这些菌株构建靶向抗菌筛选平台。结果建立了针对72个菌体生长的必需基因,10余个途径的全细胞筛选模型,形成可全面评价化合物活性位点的模型体系。对已知药物进行了模拟筛选和靶点评价,证实了筛选体系的可靠性。结论利用本文建立的筛选体系,可完成抗革兰阴性菌靶向药物筛选和机制评价两个功能。
[Abstract]:Objective to establish a comprehensive model system for screening new drugs against Gram-negative bacteria. Methods DH5 伪 strain of Escherichia coli was used as the model strain of Gram-negative bacteria. Antisense RNA silencing technique was used to specifically reduce the expression level of target gene, and a series of antisense RNA low expression strains were constructed, and the target antibacterial screening platform was constructed based on these strains. Results A whole cell screening model was established for 72 essential genes and more than 10 pathways to evaluate the active sites of compounds. The simulation screening and target evaluation of known drugs confirmed the reliability of the screening system. Conclusion the screening system established in this paper can be used to screen Gram-negative bacteria and evaluate its mechanism.
【作者单位】： 上海来益生物药物研究开发中心有限责任公司;上海交通大学;
【基金】：国家重大新药创制专项(No.2012ZX09301002-003)
【分类号】：R978
本文编号：2346335
[Abstract]:Objective to establish a comprehensive model system for screening new drugs against Gram-negative bacteria. Methods DH5 伪 strain of Escherichia coli was used as the model strain of Gram-negative bacteria. Antisense RNA silencing technique was used to specifically reduce the expression level of target gene, and a series of antisense RNA low expression strains were constructed, and the target antibacterial screening platform was constructed based on these strains. Results A whole cell screening model was established for 72 essential genes and more than 10 pathways to evaluate the active sites of compounds. The simulation screening and target evaluation of known drugs confirmed the reliability of the screening system. Conclusion the screening system established in this paper can be used to screen Gram-negative bacteria and evaluate its mechanism.
【作者单位】： 上海来益生物药物研究开发中心有限责任公司;上海交通大学;
【基金】：国家重大新药创制专项(No.2012ZX09301002-003)
【分类号】：R978
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