Luciferin Amides Enable in Vivo Bioluminescence Detection of Endogenous Fatty Acid Amide Hydrolase Activity
| Autor: | David M. Mofford, Stephen C. Miller, Spencer T. Adams, Gadarla Randheer Reddy, G. S. Kiran Kumar Reddy |
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| Rok vydání: | 2015 |
| Předmět: |
Pyridines
Photoprotein CHO Cells 010402 general chemistry 01 natural sciences Biochemistry Catalysis Amidohydrolases Mice Cricetulus Colloid and Surface Chemistry Piperidines Luciferases Firefly Fatty acid amide hydrolase Animals Humans Bioluminescence imaging Bioluminescence Tissue Distribution Luciferase Benzothiazoles Enzyme Inhibitors Enzyme Assays chemistry.chemical_classification Luminescent Agents 010405 organic chemistry Communication Hydrolysis Optical Imaging Fatty acid General Chemistry Amides Luciferin 0104 chemical sciences 3. Good health Enzyme chemistry lipids (amino acids peptides and proteins) HeLa Cells |
| Zdroj: | Journal of the American Chemical Society |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.5b04357 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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