Tocris Bioscience Extends Range of Light-Sensitive Caged Compounds Developed by Columbia University
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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 tool for studying molecular mechanisms, as pre-determined amounts of such molecules can be delivered at precise, controllable time points.
RuBi-Glutamate, a ruthenium-bipyridine-trimethylphosphine caged glutamate, is excited by visible wavelengths and releases glutamate, the brain’s main neurotransmitter, after one- or two-photon excitation. It possesses a high quantum efficiency and can be used at low concentrations, partly avoiding blockade of GABAergic transmission seen with other caged glutamate compounds. RuBi-Glutamate also displays high spatial resolution and generates excitatory responses in individual dendritic spines with physiological kinetics. RuBi-Glutamate is one of the fastest caged glutamate compounds yet developed, releasing glutamate in tens of nanoseconds.
RuBi-4AP, a water soluble ruthenium-bipyridine-triphenylphosphine caged 4-aminopyridine (4-AP), is also excited by visible wavelengths and has two-photon uncaging capabilities under physiological conditions. RuBi-4AP releases 4-AP, a voltage-dependent K+ channel blocker. These channels control synaptic release and are crucial for the normal functioning of the nervous system.
“Compared to currently available ultraviolet (UV) light-sensitive caged compounds, RuBi-Glutamate and RuBi-4AP, along with the previously licensed RuBi-GABA, can all be uncaged using longer wavelengths of light, e.g. blue or even green light,, resulting in less scattering and allowing the light source to penetrate deeper into living tissue. This could be key for their future use in vivo,” says 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 and a co-inventor of the technology, along with colleague Dr. Roberto Etchenique, a professor in the Department of Inorganic Chemistry at the University of Buenos Aires.
Duncan Crawford, Tocris’ Chief Scientific Officer, says, “We know that there is a great deal of interest in caging technology from the global research community. By making these novel products available to scientists, we hope to facilitate new and exciting discoveries in the basic mechanisms underlying fundamental biological processes.”
“Understanding these processes may also expand investigation of these compounds for clinical applications,” suggests Beth Kauderer, the licensing officer at Columbia Technology Ventures who negotiated the agreement. “4AP is now approved for treating certain neurodegenerative syndromes; it is possible that caged 4AP compounds may be employed for more selective, safer therapies.”