Lead Inventors:
Dalibor Sames, Ph.D.; Gong Chen; Dominic J. Yee; Niko G. Gubernator
Enzyme monitoring for neurological and psychiatric disease therapy:
Monoamine oxidases (MAOs) are enzymes that catalyze the aerobic oxidation of amine substrates to the corresponding imines. These enzymes play an important role in the central and peripheral nervous systems. Since altered levels of MAO activity have been associated with many neurological and psychiatric diseases, there is a need for a direct and sensitive technique for imaging MAO activity in intact cells and tissues.
Drug screening and real-time monitoring of central nervous system enzyme activity:
The technology is an efficient and selective fluorogenic reporter substrate for MAO-A and MAO-B. This substrate is based upon 6-aminocoumarin modified with an aminoethyl side chain. The technology relies upon a redox switch based on a sequence of oxidation and intramolecular cyclization to effect rapid fluorogenic switching when MAO acts upon the substrate. The substrate was successfully tested with MAO-A in human placental mitochondria and with MAO-B in beef liver mitochondria.
Applications:
-- The technology can be used for real-time monitoring of MAO activity (e.g., in neurotransmission) in intact neural tissue.
-- The technology can be used for drug screening.
Advantages:
-- The technology highlights enzyme activity with greater sensitivity than other fluorogenic substrates because it emits at a range farther away from regions of autofluorescence.
Patent Status: Patent Pending (US20100035279) ~ see link below.
Licensing Status: Available for License
Publications:
Design of Optical Switches as Metabolic Indicators: New Fluorogenic Probes for Monoamine Oxidases (MAO A and B), J. Am. Chem. Soc., Vol. 127, No. 13, pp. 4544-4545, 2005.