Modified peptides as potent inhibitors of the PSD-95/NMDA receptor interaction
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United States of America Patent
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Feb 27, 2018
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Dec 16, 2015
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Jul 9, 2008
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Abstract
The present invention is directed to the provision of small molecule inhibitors of the PSD-95/NMDA receptor interaction, employing an undecapeptide corresponding to the C-terminal of the NMDA as a template for finding lead candidates. A compound (NMDAR/PSD-95 inhibitor) of the invention includes a peptide or peptide analog comprising at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analog thereof, and X is selected from among A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analog thereof, wherein an amino-terminal residue of the peptide is N-alkylated. Alternatively the compound of the invention comprises a first peptide or peptide analog linked to a second peptide or peptide analog by a linker, where the first and second peptide or peptide analog each comprise at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analog thereof, and X is selected from among A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analog thereof.
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