Postsynaptic density protein-95 (PSD-95)/Discs-large/ZO-1 (PDZ) domains play an essential role in the regulation of intracellular signaling involved in neuronal disease and cancer. Tat-NR2B9c is a 20-mer peptide consisting of nine C-terminal amino acids of the NMDA NR2B subunit. It inhibits PSD-95 domain 1 and PSD-95 domain 2 with EC50 values of 670 nM and 6.7 nM, respectively. The IC50 values for Tat-NR2B9c inhibiting the interactions between NMDAR2A, NMDAR2B, NMDAR2C and PSD-95 are 0.5, 8, and 0.75μm, respectively. Tat-NR2B9c also inhibits the interaction between neuronal nitric oxide synthase and PSD-95 with an IC50 value of 0.2μm[3]. In NMDA-treated neuronal cultures, Tat-NR2B9c at 0.5µM suppressed NMDA-induced superoxide production by 75%. The NMDA-type glutamate receptor-triggered NOX2 activation and DNA damage were also prevented by Tat-NR2B9c at 0.5µM[4]. In mice subjected to temporary middle cerebral artery occlusion (tMCAO) for 30 and 60 min, treatment with 10nmol/g Tat-NR2B9c significantly decreased infarct volumes by 24.5% and 26.0%, respectively[5].
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