Caged Compounds: Synthesis & Application of Double-caged GABA and Glutamate

Abstract

Though methods of probing neural activity such as microelectrode stimulation have been widely used, caged compounds have emerged as an improved technique for achieving rapid, highresolution chemical stimulation through optical means. Caged compounds are neurotransmitters modified with a photoactive protecting group (“cage”), which undergoes autocleavage upon light exposure. An extension of this technique—termed chemical two-photon uncaging—adds two cage groups to the substrate, conferring the additional advantages of non-linear spatial resolution as well biological inertness before light exposure. The current project synthesizes two forms of double-caged compounds: bis-CNB-GABA and bis-CDNI-glutamate. The former is a significant improvement over previously developed caged GABAs because it is less antagonistic before photolysis, while the latter takes advantage of two-photon uncaging to produce an unprecedented four-photon relationship of substrate release and light exposure.