high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage

Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lac...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS 2012-02, Vol.109 (9), p.3317-3322
Hauptverfasser:	Bach, Anders, Clausen, Bettina H, Møller, Magda, Vestergaard, Bente, Chi, Celestine N, Round, Adam, Sørensen, Pernille L, Nissen, Klaus B, Kastrup, Jette S, Gajhede, Michael, Jemth, Per, Kristensen, Anders S, Lundström, Patrik, Lambertsen, Kate L, Strømgaard, Kristian
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Sequence Animals Behavioral neuroscience Binding Sites Biological Sciences Blood Blood brain barrier blood plasma Brain damage Brain injury Crystallography, X-Ray Disks Large Homolog 4 Protein Drug Design drug discovery Drug Evaluation, Preclinical Drug interactions dynamic models enzyme inhibitors Glutamic acid receptors Glutamic acid receptors (ionotropic) Guanylate Kinases - antagonists & inhibitors Humans infarction Infarction, Middle Cerebral Artery - complications Infarction, Middle Cerebral Artery - drug therapy Infarction, Middle Cerebral Artery - pathology Intracellular Signaling Peptides and Proteins - antagonists & inhibitors Intravenous administration intravenous injection Ischemia ischemic stroke Learning Disorders - etiology Learning Disorders - prevention & control Ligands Male Membrane Proteins - antagonists & inhibitors Mice Mice, Inbred C57BL Models, Molecular Molecular Sequence Data Molecular Targeted Therapy Movement Disorders - etiology Movement Disorders - prevention & control N-Methyl-D-aspartic acid receptors N.M.R Neuroprotective agents Neuroprotective Agents - chemical synthesis Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use neuroprotective effect Nitric-oxide synthase nuclear magnetic resonance spectroscopy Nuclear Magnetic Resonance, Biomolecular Oxides PDZ Domains - drug effects Peptides - chemical synthesis Peptides - pharmacology Peptides - therapeutic use Plasma stability postsynaptic density Postsynaptic density proteins Postural Balance Protein Conformation Protein folding protein-protein interactions Proteins Receptors Rodents Sensation Disorders - etiology Sensation Disorders - prevention & control Stroke Strokes TECHNOLOGY TEKNIKVETENSKAP X-radiation X-ray crystallography X-ray diffraction X-ray scattering
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