發(fā)布時間：2018-11-21 07:39

【摘要】：目的建立靶向篩選抗革蘭陰性菌新藥的綜合模型體系。方法以大腸埃希菌DH5α菌株作為革蘭陰性菌的模式菌,利用反義RNA沉默技術(shù)特異性降低靶基因的表達水平,構(gòu)建系列反義RNA低表達菌株,并基于這些菌株構(gòu)建靶向抗菌篩選平臺。結(jié)果建立了針對72個菌體生長的必需基因,10余個途徑的全細胞篩選模型,形成可全面評價化合物活性位點的模型體系。對已知藥物進行了模擬篩選和靶點評價,證實了篩選體系的可靠性。結(jié)論利用本文建立的篩選體系,可完成抗革蘭陰性菌靶向藥物篩選和機制評價兩個功能。
[Abstract]:Objective to establish a comprehensive model system for screening new drugs against Gram-negative bacteria. Methods DH5 偽 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.
【作者單位】： 上海來益生物藥物研究開發(fā)中心有限責(zé)任公司;上海交通大學(xué);
【基金】：國家重大新藥創(chuàng)制專項(No.2012ZX09301002-003)
【分類號】：R978

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