Brominated luciferins are versatile bioluminescent probes

摘要

We report a set of brominated luciferins for bioluminescence imaging. These regioisomeric scaffolds were accessed using a common synthetic route. All analogs produced light with firefly luciferase, although varying levels of emission were observed. Differences in photon output were analyzed via computation and photophysical measurements. The “brightest” brominated luciferin was further evaluated in cell and animal models. At low doses, the analog outperformed the native substrate in cells. The remaining luciferins, while weak emitters with firefly luciferase, were inherently capable of light production and thus potential substrates for orthogonal mutant enzymes.