细菌感染新型荧光共振能量转移探针的设计、合成及应用研究

Our project aims to develop specific tools for non-invasive imaging of bacterial infections related molecular events. These fluorescent probes allow real time imaging of protease activity throughout reduction or/and increase of fluorescence resonance energy transfer (FRET). In particular, developing dual FRET reporters for the real-time visualization of bacteria membrane-associated transpeptidase (sortase A) bifunctions, we will also translate established strategies in medicinal chemistry to design highly selective SMART probes and optimize the bacteria specificity of probes integrating concepts from bacteria membrane targeted drug delivery. Such probes can be adopted for use in non-invasive whole body bacterial infections imaging applications, which are of high relevance for disease detection, monitoring of disease progression and evaluating novel therapies.

本项目拟通过"reversed design"或药物化学的方法研制和开发新型荧光共振能量转移（FRET）分子探针，对金黄色葡萄球菌转肽酶Sortase A的水解及催化聚合双功能进行检测。在此基础上，开展第二代细菌靶向性探针分子研发，既通过在探针分子中引入细胞膜靶向基团，使得探针分子在细菌表面富集，实现信号放大与增强，而后运用相类似的设计原理研发多种细菌感染相关蛋白水解酶FRET探针分子。此类新型细菌靶向性FRET探针分子将在细菌细胞水平上实现酶的分子成像，为细菌感染诊断和抗生物膜药物研发提供检测平台，并为后续活体成像研究、细菌感染临床早期诊断奠定基础。

本项目通过"reversed design"或药物化学的方法研制和开发新型荧光共振能量转移（FRET）分子探针，对金黄色葡萄球菌硝基还原酶、SspA和转肽酶Sortase A的水解及催化聚合双功能进行检测。在此基础上，开展第二代细菌靶向性探针分子研发，既通过在探针分子中引入细胞膜靶向基团，使得探针分子在细菌表面富集，实现信号放大与增强，而后运用相类似的设计原理研发多种细菌感染相关蛋白水解酶FRET探针分子。此类新型细菌靶向性FRET探针分子将在细菌细胞水平上实现酶的分子成像，为细菌感染诊断和抗生物膜药物研发提供检测平台，并为后续活体成像研究、细菌感染临床早期诊断奠定基础。