| http://purl.uniprot.org/citations/22343531 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22343531 | http://www.w3.org/2000/01/rdf-schema#comment | "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 lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1113761109"xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Gajhede M."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Bach A."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Round A."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Moller M."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Kastrup J.S."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Jemth P."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Kristensen A.S."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Vestergaard B."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Stromgaard K."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Lambertsen K.L."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Lundstrom P."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Clausen B.H."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Chi C.N."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Nissen K.B."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/author | "Sorensen P.L."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/pages | "3317-3322"xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/title | "A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage."xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://purl.uniprot.org/core/volume | "109"xsd:string |
| http://purl.uniprot.org/citations/22343531 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22343531 |
| http://purl.uniprot.org/citations/22343531 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22343531 |