Newswise — Ascent Scientific and Columbia University today announced that they have entered into a license agreement for RuBi-Glutamate, RuBi-GABA and RuBi-4AP, novel light-sensitive, caged ligands that have broad applicability for biological research.
Caged compounds consist of a bioactive molecule (the ‘caged’ compound) that is temporarily inactivated by being bound to a chemical group (the “cage” moiety). By breaking this bond with light, the bioactive molecule can be “uncaged” and activated.
The range of RuBi compounds being licensed from Columbia can be activated by visible wavelengths of light – offering many advantages over previously available caged compounds. There is no need to use harmful UV light (which is deleterious to living tissues), the equipment does not require expensive quartz optics and uncaging can occur at much faster speeds due to the single photochemical step involved in the light-sensitive uncaging process.
RuBi-Glutamate a novel caged-glutamate compound based on ruthenium photochemistry, is excited with visible wavelengths and releases glutamate after one- or two-photon excitation. It has high quantum efficiency and can be used at low concentrations. It enables the photoactivation of neuronal dendrites and circuits with visible or two-photon light sources, achieving single-cell, or even single-spine, precision. It is one of the fastest caged glutamate compounds yet developed, releasing glutamate in tens of nanoseconds. Its quantum efficiency is also one of the highest, more than 0.1 at physiological pH.
RuBi-GABA is a novel caged-GABA compound that uses a ruthenium complex as photosensor. It can be excited with visible wavelengths, providing greater tissue penetration, less photo-toxicity, and faster photorelease kinetics than other UV light-sensitive caged compounds. Like all RuBi coumpounds, RuBi-GABA also can be released with two-photon excitation. Potential uses include GABA receptor mapping, and optical silencing of neuronal firing, including optical blockade of epilepsy.
RuBi-4AP is a water soluble caged 4-aminopyridine (4-AP) based on ruthenium photochemistry. It is excited by visible wavelengths and has two-photon uncaging capabilities under physiological conditions. RuBi-4AP releases the voltage-dependent K+ channel blocker 4-aminopyridine (#Asc-122) when uncaged and can be used to optically trigger epileptic seizures.
“This family of ruthenium caged compounds can greatly advance research in different fields of biology, such as neuroscience, cell and developmental biology and possibly also cancer biology, by enabling the optical manipulation of a variety of cellular functions with visible light and two-photon lasers,” says Dr. 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 is a co-inventor of the compounds, with his collaborator Dr. Roberto Etchenique, a professor in the Department of Inorganic Chemistry at the University of Buenos Aires. Drs. Yuste and Etchenique report, “RuBi-Glutamate, RuBi-GABA and Rubi-4AP are the first three of a series of compounds that we are developing and testing to provide a toolbox for optical experiments on living tissue.”
Steve Roome, Ascent Scientific’s Commercial Director comments, “We are hugely excited about these new ligands and their potential to facilitate important scientific investigation and discovery. The technologies are already proven tools for basic science research applications, as evidenced by recent publications from the laboratories of Drs. Yuste and Etchenique.
“We are very pleased to be partnering with Ascent Scientific for the distribution of our RuBi compounds worldwide,” says Beth Kauderer of Columbia Technology Ventures, the technology transfer office of Columbia University. “Working with Ascent, we hope to make these compounds widely accessible and available for basic and translational research and discovery.”
References:Fino et al (2009) RuBi-Glutamate: Two-Photon and Visible-Light Photoactivation of Neurons and Dendritic spines. Front Neural Circuits. 2009;3:2. Nikolenko et al (2005) Two-photon uncaging of neurochemicals using inorganic metal complexes. Chem Commun 7:1752-4. Salierno et al (2010) A fast ruthenium polypyridine cage complex photoreleases glutamate with visible or IR light in one and two photon regimes. J Inorg Biochem. 104:418-22. Verde et al (2008) Photorelease of GABA with Visible Light Using an Inorganic Caging Group. Front Neural Circuits. 2:2.Zayat et al (2003) A new strategy for neurochemical photodelivery: metal-ligand heterolytic cleavage. J Am Chem Soc. 125:882-3. Zayat et al (2007) A new inorganic photolabile protecting group for highly efficient visible light GABA uncaging. Chembiochem. 8:2035-8.
About Columbia Technology VenturesA leading academic and research university, Columbia University 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, Columbia Technology Ventures, manages Columbia's intellectual property portfolio and serves as the university's gateway for companies and entrepreneurs seeking novel technology solutions. Our core mission is to facilitate the transfer of inventions from academic research to outside organizations for the benefit of society on a local, national and global basis. For more information on Columbia Technology Ventures, please visit www.techventures.columbia.edu.
About Ascent ScientificAbout Ascent Scientific Ascent Scientific offers a range of high quality receptor ligands and synthetic chemistry services at competitive prices. Our Low-Cost LigandsTM range of products includes receptor ligands and signaling tools for research in areas such as glutamate, GABA, ion channels, cannabinoids, opioids, 5-HT and more. We also offer cost-effective custom synthesis of a wide range of chemical entities, including organic molecules, fluorescent labels, standards and references, stable isotope labels, and receptor ligands.
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