稀土金属配合物发光具有大斯托克位移，发射光谱特异易识别，发光稳定且寿命长，生物体内化学活性低等优点。以1，4，7，10-四氮杂环十二烷（Cyclen）为骨架设计稀土配合物，我们实现对细胞周期关键调控蛋白CyclinA， Plk1等特异靶点的活细胞显微成像。在此基础上，本项目设计的先导配合物HGEu001能特异地靶向真核细胞的纤毛——细胞表面向外伸出的细长突起结构，与细胞应激，细胞分裂，干细胞极性等相关。在不需要细胞转染或抗体标记的情况下，实现纤毛的活细胞成像和实时追踪。以HGEu001为分子探针，我们旨在揭示该配合物的纤毛蛋白靶点和结合方式，实现线毛在细胞应激下的生长，侧向等实时观察和三维立体成像，并探究配合物与靶点蛋白结合的晶体结构，明了结合区域的关键基团和作用方式，揭示可能的设计原理，并以此改进和优化配合物，为稀土配合物应用于活细胞特异靶点的结合与显微成像及生物医学功能研究等提供新思路

Rare earth metal complexes have large Stokes shift, characteristic emission spectrum, long luminescence lifetimes and stable emission, low chemical activity in organisms. Taking use of 1, 4, 7, 10-tetraazacyclododecane (Cyclen) as the framework for design of rare earth complexes, we realized the live cell imaging of key cell cycle regulators such as CyclinA, Plk1. On this basis, the project designs a leading complex – HGEu001 that capable of specific targeting to eukaryotic cell primary cilium. Primary cilium is a slender structure protruding from the cell surface, and regulates the cellular stress, cell division, or stem cell polarity, etc. Without cell transfection or antibody labeling, we realized the live cell imaging and real-time tracking of cilia. Using HGEu001 as a molecular probe, we aim to reveal the protein targets of the complex and the way of combination, and also perform the real-time observation and three-dimensional imaging of primary cilium in the situation of cellular stress or lateral movement. We will further explore the crystal structure of the complex with its target protein, understand the way of binding and the residues involved. With the above work, we may reveal a possible principle for rational design of rare earth complex, and contribute to the optimization of the rare earth complexes for specific targeting and responsive emission in living cells that in hope of providing new ideas and design methods for biomedical research.