-95 - HIGH-AFFINITY DIMERIC INHIBITORS OF PSD-95 AS EFFICIENT NEUROPROTECTANTS AGAINST ISCHEMIC BRAIN DAMAGE AND FOR TREATMENT OF PAIN

摘要

The present invention provides a pharmaceutical composition comprising a novel potent inhibitor of ternary protein complexes of nNOS, PSD-95 and NMDA receptors, and said inhibitor for the prevention and / or treatment of excitatory-related diseases and chronic pain conditions in a subject. To provide. The inhibitor is a dimeric PSD-95 inhibitor comprising a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, wherein the first and second peptide or peptide analogues have at least 4 having the sequence YTXV or YSXV Amide-linked moieties, a. Y is selected from E, Q and A, or analogs thereof, b. X is selected from A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D and N-Me-N, or analogs thereof, wherein the cell permeable peptide (CPP) is a linker Or the amino acid side chains of the first and second peptides or peptide analogs. The linker may be a PEG or NPEG linker.