基于光亲和小分子探针技术的海洋天然活性分子Baculiferin抗HIV作用机制研究

The development of anti-HIV drug molecules with new targets is a worldwide globe focus in the international scientific community. The Vif/APOBEC3G signaling pathway is the latest and most promising anti-HIV drug target. Our laboratory has discovered previously a novel alkaloids from sponges,called Baculiferin, which had high anti-HIV activity and the underlying mechanism could be Vif/APOBEC3G targeted. We get a hypothesis that this class of compounds inhibits the interaction of Vif/APOBEC3G to role as anti-HIV agent. Firstly, this project intends to verify the targeting action of Vif/APOBEC3G using the photo-affinity probe approach. Secondly, other potential novel targets during the infection process could be studied. The aim of this project is to improve the understanding on the anti-HIV mechanism of Baculiferin alkaloids, while to provide a novel structure scaffold in the research and development of anti-HIV marine drug.

研发具有新型作用靶点的抗HIV药物分子一直是国际科学界研究的热点，Vif/APOBEC3G信号通路是最新且极具潜力的抗HIV研究靶点。课题组前期研究发现从海绵中分离鉴定的Baculiferin类生物碱具有较强的抗HIV活性，且此活性极有可能具有Vif/APOBEC3G靶向性。因此，本课题提出假设此类生物碱是通过抑制Vif/APOBEC3G的结合发挥抗HIV活性的。为了验证此假设，设计了利用光亲和小分子探针技术，对该类生物碱的Vif/APOBEC3G靶蛋白进行验证，并希望对其结合位点进行系统阐明。同时对病毒感染宿主细胞过程中的其他潜在新颖靶点进行研究。完善Baculiferin类生物碱的抗HIV作用机制的研究，为新型抗HIV海洋药物的研发提供分子模型基础。