N-NMOC-L-GLUTAMATE, A NEW CAGED GLUTAMATE WITH HIGH CHEMICAL-STABILITY AND LOW PRE-PHOTOLYSIS ACTIVITY

We report the synthesis, the physicochemical characterization, and bio logical evaluation of a new caged glutamate, N-(o-nitromandelyl)oxycar bonyl-L-glutamic acid (Nmoc-Glu), that liberates free glutamate on pho tolysis. The low affinity of certain glutamate receptors and their rap id entry into desensitization have effectively prevented the creation of an ideal caged glutamate, In the absence of an ideal compound, Nmoc -Glu was designed to resist spontaneous hydrolysis while maintaining r easonable photorelease yield and kinetics, Chemical and physiological analyses reveal that Nmoc-Glu, indeed, has exceptionally low residual activity and high chemical stability, The quantum yield of Nmoc-Glu is 0.11, Photolytic uncaging and release of free glutamate occur in two steps, consisting of an initial light-induced cleavage that proceeds o n the sub-millisecond time scale, and a subsequent light-independent, pH-dependent decarboxylation step that proceeds on the millisecond tim e scale, The low residual activity and high chemical stability of Nmoc -Glu are important advantages in applications where pre-photolysis Glu receptor activation and desensitization must be minimized.