N-Methyl-d-aspartate (NMDA) is an excitotoxic amino acid used to identify a specific subset of glutamate receptors. The activity of NMDA receptors is closely related to the redox level of the biological system. Glutathione (GSH) as an antioxidant plays a key role with regard to modulation of the redox environment. In this work we designed and developed a GSH-specific fluorescent probe with the capability of targeting NMDA receptors, which was composed of a two-photon naphthalimide fluorophore, a GSH-reactive group sulfonamide, and an ifenprodil targeting group for the NMDA receptor. This probe exhibited high selectivity toward GSH in comparison to other similar amino acids. Two-photon fluorescence microscopy allowed this probe to successfully monitor GSH in neuronal cells and hippocampal tissues with an excitation at 750 nm. It could serve as a potential practical imaging tool to explore the function of GSH and related biological processes in the brain.
The authors appreciate Prof. Sang-Jip Nam and Eun-Young Lee (Department of Chemistry and Nano Science, Ewha Womans University) for providing HPLC analysis. This study was supported financially by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2012R1A3A2048814 for J. Yoon and No. 2019R1A2B5B03100278 for H. M. Kim). J. Yin acknowledges financial support from the National Natural Science Foundation of China (21676113, 21772054); Distinguished Young Scholar of Hubei Province (2018CFA079); Supported by the 111 Project B17019; Supported by the Scholar support program of CCNU (0900-31101090002). The Korea Basic Science Institute (Western Seoul) is acknowledged for the LC/MS data. FAB mass spectral data were obtained from the Korea Basic Science Institute (Daegu) on a Jeol JMS 700 high resolution mass spectrometer.
