Synthesis and photolytic evaluation of a nitroindoline-caged glycine with a side chain of high negative charge for use in neuroscience

A photolabile precursor of the neuroinhibitory amino acid glycine has been synthesised with two phosphate groups attached to the indoline nucleus at a 4-alkoxy substituent. In common with the photochemical properties of other 1-acyl-7-nitroindolines, this releases glycine on a sub-μs time scale upon irradiation with near-UV light. The synthetic route previously developed for the preparation of the GABA analogue required some modifications because of the greater hydrolytic sensitivity of the glycine compound. The phosphorylation method used here could be beneficial to the synthesis of other nitroindoline-caged amino acids, especially the related caged GABA derivative. Glycine released by laser photolysis on spinal cord neurons generated fast-rising responses and the pharmacological properties of the reagent are such that it is useful for physiological experiments.