Bioluminescence is a widely used imaging technology, with applications ranging from gene sequencing to whole animal imaging. At the heart of this technology are enzymes (luciferases) that catalyze the oxidation of small molecule substrates (luciferins), releasing photons of light in the process. While several luciferase-luciferin pairs are known to exist in nature, relatively few have been developed for routine application in biomedical research. To expand the palette of bioluminescent probes, we aimed to develop artificial luciferins with unique heterocyclic cores. We synthesized regioisomeric luciferins bearing thiazolo-pyridyl groups using a highly modular route involving a Pd-catalyzed oxidative cyclization. The luciferin analogs were shown to emit light when incubated with either recombinantly produced luciferase or luciferase-expressing mammalian cells. Notably, the luciferins emitted distinct colors of light. These wavelenghts could be spectrally resolved in cellular imaging experiments using select filter sets. Collectively, our results suggest that pyridone luciferins are suitable for multi-component imaging applications.

Design and synthesis of pyridone luciferins for bioluminescence imaging

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.