Bright Ideas for Chemical Biology.pdfVIP

NIH Public Access Author Manuscript ACS Chem Biol . Author manuscript; available in PMC 2010 January 6. N Published in final edited form as: I H ACS Chem Biol . 2008 March 20; 3 3 : 142–155. doi:10.1021/cb700248m. - P A A u Bright Ideas for Chemical Biology t h o r ?,? ?,§,* M Luke D. Lavis and Ronald T. Raines a Departments of Chemistry and Biochemistry, University of Wisconsin–Madison, Madison, WI 53706 n u s c Abstract r i p t Small-molecule fluorescent probes embody an essential facet of chemical biology. Although numerous compounds are known, the ensemble of fluorescent probes is based on a modest collection of modular “core” dyes. The elaboration of these dyes with diverse chemical moieties is enabling the precise interrogation of biochemical and biological systems. The importance of fluorescence- based technologies in chemical biology elicits a necessity to understand the major classes of small- molecule fluorophores. Here, we examine the chemical and photophysical properties of oft-used fluorophores, and highlight classic and contemporary examples in which utility has been built upon N I these scaffolds. H - P A A Introduction u t h Small fluorescent molecules are indispensable tools for chemical biology, being ubiquitous as o r biomolecular labels, enzyme substrates, environmental indicators, and cellular stains 1–12 . M Choosing a suitable fluorophore to visualize a biochemical or biological process can be a n daunting, given the countless molecules available either commercially 13 or through de u s novo design and synthesis. Fortunately, the plethora of fluorescent probes has an intrinsic c r modularity. Attachment of various reactive groups, substrate moieties, chelating components, i p and other chemical entities to a small number of “core” fluorophores gives rise to the ensemble t of extant probes. Overall, these core fluorophores are well-established 9,14 , consisting of molecules with excellent spectral characteristics, high chemical stabiliti