Department of Biochemistry and Molecular Pharmacology
Biochemistry | Chemistry | Enzymes and Coenzymes
Firefly luciferase is homologous to fatty acyl-CoA synthetases. We hypothesized that the firefly luciferase substrate d-luciferin and its analogs are fatty acid mimics that are ideally suited to probe the chemistry of enzymes that release fatty acid products. Here, we synthesized luciferin amides and found that these molecules are hydrolyzed to substrates for firefly luciferase by the enzyme fatty acid amide hydrolase (FAAH). In the presence of luciferase, these molecules enable highly sensitive and selective bioluminescent detection of FAAH activity in vitro, in live cells, and in vivo. The potency and tissue distribution of FAAH inhibitors can be imaged in live mice, and luciferin amides serve as exemplary reagents for greatly improved bioluminescence imaging in FAAH-expressing tissues such as the brain.
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This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
DOI of Published Version
J Am Chem Soc. 2015 Jul 15;137(27):8684-7. doi: 10.1021/jacs.5b04357. Epub 2015 Jul 2. Link to article on publisher's site
Journal of the American Chemical Society
Mofford, David M.; Adams, Spencer T. Jr; Reddy, G. S. Kiran Kumar; Reddy, Gadarla Randheer; and Miller, Stephen C., "Luciferin Amides Enable in Vivo Bioluminescence Detection of Endogenous Fatty Acid Amide Hydrolase Activity" (2015). Open Access Articles. 2691.