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PREVINS AS SPECIFIC INHIBITORS AND THERAPEUTIC AGENTS FOR BOTULINUM TOXIN B AND TETANUS NEUROTOXINS
The compounds of the invention are generally described by the formula: B.sub.1Z*.sub.2B.sub.3Z*.sub.4X*.sub.5Q.sub.6F.sub.7X.sub.8X.sub.9X.sub.1- 0X.sub.11, (1) B.sub.1X.sub.2X.sub.3X.sub.4X.sub.5Q.sub.6F.sub.7X.sub.8X.sub.9X.sub.10X.- sub.11, or (2) B.sub.1Z.sub.2B.sub.3X.sub.4Z.sub.5Q.sub.6F.sub.7Z.sub.8X.sub.9X.sub.10X.- sub.11 (3) and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic of polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large of hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum b and tetanus toxins.
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Inventor(s):GORDON, R.; MOORAD, D.; DOCTOR, B.; GARCIA, G.