Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), 138667 Singapore, Singapore.
Curr Opin Chem Biol. 2010 Jun;14(3):383-9. doi: 10.1016/j.cbpa.2010.02.020. Epub 2010 Mar 12.
Diversity-oriented fluorescence library approaches have significantly accelerated the development of new sensors. By making use of combinatorial chemistry and high-throughput screening, they can circumvent our limitations in designing probes for particular recognition processes. Combinatorial chemists have proved how to derivatize fluorogenic scaffolds, tune their photophysical spectra and adjust their properties (from cell permeability to quantum yields) to generate libraries of potential sensors. Several platforms (in vitro assays, cell-based imaging) have also been optimized to screen these libraries in a high-throughput manner, and with the recent progress in image acquisition and analysis, their scope has been expanded toward more diverse and demanding biological systems. Supported by successful examples of fluorescent sensors for biomolecules, proteins, or even phenotypes, this review (together with a video abstract) stresses the important role that diversity-oriented approaches will continue to play in probe development in the near future.
导向多样性的荧光文库方法极大地加速了新型传感器的发展。通过利用组合化学和高通量筛选，它们可以避免我们在设计针对特定识别过程的探针方面的局限性。组合化学家已经证明了如何衍生荧光团支架，调整其光物理光谱，并调整其性质（从细胞通透性到量子产率），以生成潜在传感器的文库。几个平台（体外测定、基于细胞的成像）也已被优化，以高通量方式筛选这些文库，并且随着图像采集和分析的最新进展，其范围已经扩展到更多样化和更具挑战性的生物系统。在生物分子、蛋白质甚至表型的荧光传感器的成功实例的支持下，这篇综述（以及一个视频摘要）强调了导向多样性的方法在探针开发方面将继续发挥重要作用。
