以蓝藻果糖-1,6-二磷酸醛缩酶和水解酶为靶标的一剂双靶新型抑藻剂的合理设计与优化研究

综合运用现代分子模拟方法（包括我们发展的计算策略和方法）、分子生物学技术（克隆表达纯化、定点突变等）、光谱分析技术（荧光、圆二色谱等）、化合物合成技术等，在分子、原子乃至电子的层次上研究蓝藻光合作用卡尔文循环中偶联的关键调控酶Cy-FBA和Cy-FBPase，阐明其结构、功能、性质及其与活性调控分子的相互作用的分子机理。在此基础上，进行多轮循环的全新双靶酶抑制剂的生物合理设计、筛选与合成优化研究，以期最终获得具有高效抑制活性的全新双靶酶抑藻剂先导化合物。本项目有望为我国以光合系统中重要调控酶为新靶标的绿色农药创制工作提供一些建设性的研究思路和前期基础。

Cyanobacteria class II fructose-1,6-bisphoshate aldolase (Cy-FBA) and cyanobacteria fructose-1,6-bisphosphatase (C-FBPase) are two neighboring key regulatory enzymes in the Calvin cycle of the cyanobacteria photosynthesis system. Each of them might be taken as a potential target for designing novel inhibitors to chemically control harmful algal blooms (HABs). In the present project, based upon the structure and catalyic regulatory mechanism，a series of novel dual-targets inhibitors are scheduled to be rationally designed, synthesized, and optimized against both the Cy-FBA and Cy-FBPase for HABs chemical control, and their inhibitory activities are scheduled to be examined both in vitro and in vivo.