AI-2型细菌群体感应的小分子探针研究

AI-2 bacterial quorum sensing can provide a brand new biotarget and mechanism of action for the development of novel antibacterial agents, thus driving the emergence of ideal drugs with anti-resistant and low-toxicity profiles. It's well known that the gene regulation of AI-2 quorum sensing is still remaining controversial hitherto. Therefore, the generation of a specific probe for AI-2 quorum sensing will help us to deeply understand the mechanism of gene regulation of AI-2 quorum sensing, and contribute to the next generation of AI-2 quorum sensing inhibitors. Based on fruitful preliminary results from the last NSFC Young Investigator Grant, the current proposal will rational design a series of small molecule probes for AI-2 quorum sensing on the basis of the click conjugation of our lead compounds and fluorophore by targetting LuxPQ receptor protein. After extensive biological evaluation, this project is expected to supply a panel of toolkit molecules for regulating AI-2 quorum sensing, as well as to lay a solid foundation for furthur antibacterial drug design and development.

细菌AI-2型群体感应为新型抗菌药物的研发提供了全新的设计靶点和作用机制，使开发可抗耐药性和低毒性的抗菌药物分子成为可能，但目前群体感应信号分子AI-2的基因调控机制还没有完全得到诠释，如果能研发出特异性的识别AI-2型群体感应的探针分子，将会更深入的阐释AI-2型群体感应的调控机制，进而更加有益于AI-2型群体感应抑制剂的开发。本项目继续选定AI-2型群体感应的受体蛋白LuxPQ为靶标，结合项目申请人正在承担的青年科学基金项目中已经获得的先导化合物结构特征，根据合理分子设计的原则，采用点击化学的方法合成具有全新结构类型的AI-2型群体感应小分子探针，以期获得能研究调控AI-2型群体感应系统的工具药分子，并为进一步的抗菌药物研发奠定基础。

细菌AI-2型群体感应为新型抗菌药物的研发提供了全新的设计靶点和作用机制，使开发可 抗耐药性和低毒性的抗菌药物分子成为可能，但目前群体感应信号分子AI-2的基因调控机制还没有完全得到诠释，如果能研发出特异性的识别AI-2型群体感应的探针分子，将会深入的阐释AI-2型群体感应的调控机制，进而更加有益于AI-2型群体感应抑制剂的开发。 本项目选定AI-2型群体感应的受体蛋白LuxPQ为靶标，结合已经获得的先导化合物结构特征，根据合理分子设计的原则，合成具有全新结构类型的AI-2型群体感应小分子探针，已发现多个具有研究开发价值AI-2型群体感应抑制剂和探针分子；在Anal. Chem.、Org. Biomol. Chem.等期刊发表SCI论文12篇，获授权专利1项，为进一步的抗菌药物研发奠定基础。