Bioluminescence imaging (BLI) is one of the most widely used techniques for monitoring molecular and cellular features in live organisms.  This technology relies on the generation of visible light from the luciferase-catalyzed oxidation of small molecule luciferins.  To date, BLI has been largely restricted to monitoring one cell type or biological function at a time, owing to a lack of suitable luciferase-luciferin pairs.  We are generating an expanded set of bioluminescent tools by re-engineering firefly luciferase to accept chemically distinct luciferins.  In this work, we synthesized novel luciferin architectures utilizing a 1,2,3-dithiazole reagent known as Appel's salt.  The chemical analogs were further screened against libraries of luciferase mutants to identify unique enzyme-substrate pairs.  The bioluminescent probes generated from our work will enable the visualization of multicellular interactions in vivo.

Expedient synthesis of luciferin analogs for orthogonal bioluminescence imaging

243rd National Meeting (2012)

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