Screening of small molecular inhibitors targeting at Toxoplasma gondii autophagy-related protein TgAtg8-TgAtg3 interaction

科研成果详情

题名	Screening of small molecular inhibitors targeting at Toxoplasma gondii autophagy-related protein TgAtg8-TgAtg3 interaction
作者	Shu Xian Liu ; Yue Hu ; Xin Hu ; Feng Tan
发表日期	2016-08-08
会议录名称	中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工作者学术研讨会论文摘要集影响因子和分区
语种	英语
原始文献类型	中国会议
关键词	Toxoplasma gondii protein-protein interaction Atg8 Atg3 small-molecule inhibitor
摘要	Objective: To acquire small molecule inhibitors that could significantly reduce the proliferation of Toxoplasma gondii and have no(or low) toxicity to the human cells. Methods: Primarily, Alphascreen and SPR assays were used to detect the inhibitory activity of small molecule compounds on human LC-Atg3 、rat Atg8-Atg3 protein-protein interaction,respectively,selected compounds that had no effect on human Atg8-Atg3 interaction, thus obtained the small molecule compounds which could specifically impact on Toxoplasma gondii and have no influence in Atg8-Atg3 interaction of human cells. Meanwhile, we evaluated the specific inhibition effects of small molecule inhibitors at the level of cytology experiments: we used plaque assays and intracellular replication assays to choose the small molecule compounds that have no toxicity to host cells and further grope the concentration of the chosen inhibitors to identity their IC50. Then estimate the internal effect of Toxoplasma gondii infected mice model by drugs. Light spot experiments were applied to judge whether our drugs inhibit the interaction of TgAtg8-TgAtg3 or not by means of observing the formation of autophagosomes Atg8-PE complexes. Results: Experiments in vivo had already screened 12 small molecule inhibitors and a small molecule agonist, this 13 small molecule compounds are clinical medicines. Plaque assays indicated that 7 small molecular compounds in our lab have definitely inhibitory activity on the proliferation of Toxoplasma gondii and have no toxicity on host cells. Spot light experiments manifested that several drugs inhibit the interaction of TgAtg8-TgAtg3.Conclusion: It was illuminated preliminary that small molecule compounds reduce the proliferation of Toxoplasma gondii targeting at the interaction of TgAtg8-TgAtg3.
资助项目	supported by grants from the Natural Science Foundation of Zhejiang Province(L Q14H190003);; the Commonweal Technology Application Project Program of Zhejiang Province(2014C33161;2015C33129)
页码	1
收录类别	CNKI
文献类型	会议论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/134396
专题	基础医学院（机能实验教学中心）_病原生物学与免疫学系_医学寄生虫学温州医科大学
作者单位	1.Department of Parasitology in Wenzhou Medical University 2.Institute of Tropical Medicine in Wenzhou Medical University
推荐引用方式 GB/T 7714	Shu Xian Liu,Yue Hu,Xin Hu,et al. Screening of small molecular inhibitors targeting at Toxoplasma gondii autophagy-related protein TgAtg8-TgAtg3 interaction[C],2016:1.

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