宿主细胞的APOBEC3G（A3G）蛋白能够破坏逆转录病毒DNA的复制，具有极强的抗HIV-1病毒的活性。HIV-1病毒的Vif蛋白能够结合A3G蛋白，形成Vif-A3G蛋白复合物，介导A3G蛋白的泛素化降解，破坏宿主的天然免疫功能。目前Vif-A3G蛋白复合物是研究宿主与病毒相互作用的重要研究对象和开发抗HIV-1病毒小分子化合物的重要靶点。 缺少高活性和作用机理明确的Vif-A3G蛋白复合物小分子探针是这一研究领域的关键问题。我们前期工作中发现了具有极高破坏Vif-A3G蛋白复合物活性和抑制HIV-1病毒活性的化合物ZBMA1104。本项目将以此为基础，设计合成多种官能团化的小分子探针，结合定量生物质谱，生物物理和生物化学方法，阐明化合物ZBMA1104的针对Vif-A3G蛋白复合物的结合位点及其作用机理，为深入理解宿主与病毒相互作用提供优秀工具化合物和研究基础。

Host protein APOBEC3G（A3G）is a potent restriction factor to HIV-1 virus by destroying viral DNA replication process. The viral protein Vif abolishes A3G function and the host innate immune system via Vif-A3G complex, in which it mediates the degradation of A3G in an ubiquitin pathway. Vif-A3G complex takes important roles in studies of host-virus interactions and development of new anti-HIV small molecules. The key challenge for these studies is the lack of potent small molecule probes with elucidated mechanism. Our previous studies identified compound ZBMA1104 that could abolish Vif-A3G complex efficiently and had strong activity to inhibit HIV-1 replication. We will study the binding site and the working mechanism of compound ZBMA1104 by designing and synthesizing functionalized small molecule probes, together with methods in biological mass spectrometry, biophysics and biochemistry. Our studies will afford good small molecule probes and solid basis to further study the host-virus interactions.