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青年导师指导能力提升计划沙龙活动——设计抗结核的新型抗生素
 

报告题目:设计抗结核的新型抗生素

报 告 人:杨海涛 教授

会议时间:2019年3月26日16:00

会议地点:威廉希尔足球官网102会议室

会议主持:侯海副教授

内容简介:Development of new antibiotics to treat tuberculosis

MmpLs (Mycobacterial membrane proteins Large) which play crucial roles in transporting lipids, polymers and immunomodulators, and that also extrude therapeutic drugs, are amongst the most important therapeutic drug targets to emerge in recent times. Here, crystal structures of Mycobacterial MmpL3 alone and in complex with four TB drug candidates including SQ109 (in Phase 2b-3 clinical trials) are reported. MmpL3 consists of a periplasmic pore domain and a twelve-helix transmembrane domain. Two Asp-Tyr pairs centrally located in this domain appear to be key facilitators of proton-translocation. SQ109, AU1235 and ICA38 bind inside the transmembrane region and disrupt these Asp-Tyr pairs. Strikingly, rimonabant, the first CB1 antagonist, was also found to target the same binding pocket. It is remarkable that rimonabant adopts completely different binding modes to inhibit mycobacterial MmpL3 and human CB1 receptor. Since MmpL3 and its orthologues are well conserved across mycobacteria and corynebacteria, these results may facilitate the development of new drugs which are broadly effective against these and other human pathogenic infectious diseases including TB, leprosy and diphtheria. In addition, this is the first report describing structures of drug candidates which can block the proton motive force to inhibit an RND family member, many of which are important targets for anti-bacterial drug discovery. These data will therefore provide inspiration for the design of new classes of antibiotics.

主讲人简介:

2006-2011耶鲁大学从事博士后研究;

2011-2013耶鲁大学Associate Research Scientist;

2013-2017天津大学教授、副院长;

2013兼任天津国际生物医药联合研究院抗感染药物研发中心主任;

2018上海科技大学免疫化学研究所Research Professor

杨海涛教授现为国家重点研发计划重点专项总体专家组成员、“973”计划青年项目首席科学家、波兰国家科学基金外审专家、国家“重大新药创制”科技重大专项评审专家和国家级人才奖励计划评审专家,获得了中国产学研合作促进奖、中国侨界贡献奖、科学中国人年度人物等荣誉。

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