Novel Light-Sensitive Caged GABA Compound

Tocris Bioscience first to launch RuBi-GABA

Bristol, UK and New York, NY - Tocris Bioscience today announced that they have entered into a licence agreement with Columbia University Science & Technology Ventures (STV) for RuBi-GABA, a novel caged-GABA compound with significant applications for basic science research.

Caged compounds are biologically-relevant molecules rendered inactive by a photolabile bond to a chemical group (the "cage"). Typically, the active molecule can be "uncaged" by breaking this bond with light, resulting in activation of the compound. Photorelease of caged bioactive molecules is a powerful tool for studying molecular mechanisms, as pre-determined amounts of such molecules can be delivered at precise, controllable time points. Photoactivated RuBi-GABA (also known as ruthenium-bipyridine-triphenylphosphine caged gamma-aminobutyric acid) triggers the release of GABA, the major inhibitory neurotransmitter in the mammalian central nervous system, often referred to as the brain's calming agent. Indeed, GABAergic modulators, such as benzodiazepine, are widely used to control epilepsy and anxiety.

RuBi-GABA has multiple advantages over other caged GABA compounds. For example, inorganic-based photorelease is usually much faster than organic approaches, and RuBi-GABA also has a high quantum yield for uncaging. Compared to currently available ultraviolet (UV) light-sensitive caged compounds, RuBi-GABA can be uncaged using longer wavelengths of light, e.g. visible light, resulting in less scattering and allowing the light source to penetrate deeper into living tissue. It has been found to produce GABA receptor-mediated currents in pyramidal neurons in vitro and does not significantly interfere with endogenous GABAergic or glutamatergic transmission. Also, RuBI-GABA can be photoreleased with two-photon lasers, affording excellent spatial resolution for uncaging. With kinetics and spatial resolution comparable to the best caged GABA compounds presently available, RuBi-GABA is likely to be at the forefront of caged GABA research.

Duncan Crawford, Tocris' Chief Scientific Officer, said, "We know that there is a great deal of interest in caging technology from the global research community. By making novel products like RuBi-GABA available through our catalog, we hope to facilitate new and exciting discoveries in the basic mechanisms underlying fundamental biological processes. For Tocris this important product adds to our comprehensive and expanding range of high purity compounds, which are used worldwide to further biomedical research. We are delighted that our relationship with Columbia University has allowed us to be able to make this material available to Life Scientists."

"Ruthenium uncaging provides greater chemical and optical flexibility and is also very stable, fast and effective with 1 and 2-photon excitation", explains Rafael Yuste, M.D., Ph.D., a professor in the Department of Biological Sciences at Columbia University and an investigator of the Howard Hughes Medical Institute. Dr. Yuste and co-inventor Dr. Roberto Etchenique, a professor in the Department of Inorganic Chemistry at the University of Buenos Aires, describe applications of the technology for GABA receptor mapping and optical silencing of neuronal firing in the August 2008 issue of Frontiers in Neural Circuits.

"RuBi-GABA is the first of a series of ruthenium-based caged compounds being developed by Dr. Yuste and his collaborators," says Beth Kauderer from STV, who negotiated the licence agreement with Tocris. "This technology will help scientists to better understand the neuronal circuitry of the brain, as well as molecular and cellular mechanisms of disease, and may lead to the development of safer and more effective therapies for epilepsy, depression and many other conditions."

View full product information on RuBi-GABA

All compounds and pharmacological data on GABA receptors can be viewed at:

References

Zayat et al (2003). A new strategy for neurochemical photodelivery: Metal-ligand heterolytic cleavage. Journal of the American Chemical Society 125 882-3.

Zayat et al (2006). Ruthenium(II) bipyridyl complexes as photolabile caging groups for amines. Inorganic Chemistry 45 1728-31.

Rial Verde et al (2008). Photorelease of GABA with visible light using an inorganic caging group. Frontiers in Neural Circuits 2.

About Columbia University

A leading academic and research university, Columbia continually seeks to advance the frontiers of knowledge and to foster a campus community deeply engaged in understanding and addressing the complex global issues of our time. Columbia University's technology transfer office, Science & Technology Ventures, (STV) serves as a bridge between Columbia's researchers and the business community. STV's core objective is to transfer inventions from the University to outside organizations and to society at large. STV at Columbia University is considered one of the leading technology transfer offices in the world, with over 300 invention disclosures from faculty, 70 licence deals and 12 new start-ups each year. For more information on STV, please visit www.stv.columbia.edu.

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