Previns as specific inhibitors and therapeutic agents for...

Details Previns as specific inhibitors and therapeutic agents for... Previns as specific inhibitors and therapeutic agents for...

C - Chemistry, Metallurgy

12

N

C12N 15/15 (2006.01) A61K 38/08 (2006.01) A61K 38/57 (2006.01) C07K 7/06 (2006.01) C07K 7/08 (2006.01) C07K 7/22 (2006.01) C07K 14/81 (2006.01) C07K 16/38 (2006.01) C12Q 1/37 (2006.01) G01N 33/53 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2372304

The compounds of the invention are generally described by the formula: (1): B1Z*2B3Z*4X*5Q6F7X8X9X10X11, (2): B1X2X3X4X5Q6F7X8X9X10X11, or (3): B1X2B3X4Z5Q6F7Z8X9X10X11 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 or 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 or 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.

L'invention concerne des composés de formule: (1): B¿1?Z?*¿¿2?B¿3?Z?*¿¿4?X?*¿¿5?Q¿6?F¿7?X¿8?X¿9?X¿10?X¿11?, (2): B¿1?X¿2?X¿3?X¿4?X¿5?Q¿6?F¿7?X¿8?X¿9?X¿10?X¿11?, ou (3): B¿1?X¿2?B¿3?X¿4?Z¿5?Q¿6?F¿7?Z¿8?X¿9?X¿10?X¿11? et leurs sels, esters, amides et formes acylées. Chaque position représentée par une lettre indique un seul résidu d'acide aminé ; B représente un acide aminé basique ou polaire/long ou sa forme modifiée; X représente un petit acide aminé hydrophobe ou sa forme modifiée; X?*¿ représente un petit acide aminé ou polaire/large ou sa forme modifiée; Z représente un acide aminé polaire/long ou hydrophobe ou; Z?*¿ représente une Proline ou un acide aminé polaire/long ou hydrophobe ou sa forme modifiée. Une des liaisons peptidiques au moins parmi les résidus d'acides aminés peu(ven)t être remplacée(s) par un analogue de liaison peptidique. Ces composés peuvent être utilisés comme blocs de construction moléculaire pour créer des composés qui sont optimisés en termes d'inhibition de l'activité protéase des toxines botuliniques de type B et tétaniques.

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