Patent Highlights June–July 2015

摘要: The postsynaptic density protein-95 (PSD95) is a scaffold anchor protein, and member of the membrane-associated guanylate kinase family. Its three PDZ domains interact with several proteins [1] including NMDA receptors also neuronal nitric oxide synthase, which itself activated by influx calcium ions through opened receptor channels.Therefore, PSD95 key facilitator glutamate-mediated neurotoxicity. Specific inhibition excitotoxicity can be achieved perturbing intracellular synthase/ PSD-95/NMDA complex using PSD-95 inhibitors. Dimeric ligands that consist peptides linked polyethylene glycol linker simultaneously bind to PDZ1 PDZ2 PSD95, such as UCCB01-125 (claimed in WO 2010/004003), have shown some effect animal models chronic pain [2], but plasma half-life these constructs very short. present invention uses modified linkers where at least one backbone oxygen atoms replaced nitrogen, fatty acid attached. This greatly enhances affinity construct human serum albumin, thereby increases its residence time without interfering substantially binding PDZs PSD95. For small molecule inhibitors see [3].