The naphthoquinone 12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo[4,5]cycloheptal[1,2-b]naphthalene-5,12-imine (TU100) was originally synthesized as a potential chemotherapeutic agent. During its characterization, however, we discovered TU100 is a potent inhibitor of luciferases, the class of enzymes responsible for bioluminescence. Luciferases are evolutionarily distinct with different structures and substrates, so it is surprising that a single compound is able to inhibit multiple forms of the enzyme. TU100 inhibits firefly, <i>Renilla</i>, and NanoLuc luciferases to varying degrees and displays either competitive or mixed inhibition with respect to the luciferin substrate. Present studies have investigated the mechanism of inhibition and evaluated the ability of TU100 to inhibit luciferase inside cells. Results reveal that TU100 is not covalently bound to the enzyme, nor is it generating reactive oxygen species causing enzyme inactivation. Tissue culture cells were transiently transfected with a <i>Renilla</i> plasmid to determine if TU100 can inhibit a luciferase expressed inside cells. Data indicate TU100 is a novel luciferase inhibitor with broad specificity against this class of enzymes. Thus, it may have utility in biological assay systems where controlling luciferase activity is important. TU100 might also be useful in the study of bioluminescence in organisms.

Turning off the lights: A novel luciferase inhibitor

249th National Meeting (2015)

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