Cell Specific Imaging Probe Development and Biomedical Applications

摘要

Bioimaging probes are reporter molecules for visualizing the cellular event. The conventional bioprobe design has been carried out by so-called hypothesis-driven approach. The basic assumption of hypothesis-driven approach is that the scientist "knows the target" in advance, and then design the recognition motif for it. An alternative approach is diversity-driven approach, in which a broad range of fluorescence molecules in a library format are constructed by combinatorial chemistry, as a tool box for unbiased screening. We have developed libraries of fluorescence small molecules by combinatorial synthesis. This Diversity Oriented Fluorescence Library Approach (DOFLA) has great advantage in terms of optical screening and target identification. The specific binding of fluorescent small molecule is readily detectable and the target protein can be tracked visibly during all the target identification processes by adding an affinity tag to the molecule. Altogether, more than 10,000 fluorescent compounds were synthesized and tested in various cell types. Using DOFLA, a broad range of colorful bioimaing probes including stem cells, microglia and pancreatic islet cells were successfully demonstrated.