High-affinity, dimeric inhibitors of PSD-95 as efficient neuroprotectants against ischemic brain damage and for treatment of pain

摘要

The invention provides novel potent inhibitors of the ternary protein complex of nNOS, PSD-95, and the NMDA receptor and pharmaceutical compositions comprising the inhibitors for prophylaxis and/or treatment of excitotoxic-related disease and chronic pain conditions in a subject. The inhibitors are dimeric PSD-95 inhibitors comprising a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, wherein the first and the second peptide or peptide analogue comprise at least four amide-bonded residues having a sequence YTXV or YSXV, wherein a. Y is selected from among E, Q, and A, or an analogue thereof, and b. X is selected from among A, Q, D, N,