Synonyms: NA-1 | Tat-NR2B9c
Compound class:
Peptide or derivative
Comment: Nerinetide (NA-1) is a peptide that was designed to target the PDZ domain of the PSD-95 protein (gene symbol DLG4) [1] to prevent its interaction with N-methyl-D-aspartate receptors (NMDARs) and neuronal nitric oxide synthase (nNOS) and block assembly of the tri-peptide complex that is a therapeutic target for the treatment of acute ischemic stroke [2-3]. Structurally, nerinetide is a 20 amino acid linear peptide that comprises nine residues derived from the COOH-terminal of the NR2B NMDAR (GluN2B; GRIN2B; that directly interacts with PSD-95's PDZ2 domain) fused to 11 amino acid cell-membrane transduction domain of the HIV-1 Tat protein (Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg; to create a cell permeable peptide). The NMDAR/nNOS/PSD-95 complex mediates neurotoxic signaling, and disruption of this function provides a neuroprotective effect that ameliorates ischemic brain damage, without inducing the negative consequences that can arise through NMDAR blockade.
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Peptide Sequence | |
H-YGRKKRRQRRRKLSSIESDV-OH | |
H-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Lys-Leu-Ser-Ser-Ile-Glu-Ser-Asp-Val-OH |
HELM Notation | |
PEPTIDE1{Y.G.R.K.K.R.R.Q.R.R.R.K.L.S.S.I.E.S.D.V}$$$$ |
Download 2D Structure | |
Canonical SMILES | Download |
Isomeric SMILES | Download |
InChI standard identifier | Download |
InChI standard key | Download |
Molecular structure representations generated using Open Babel