Use of multivalent synthetic ligands of surface nucleolin...

C - Chemistry – Metallurgy – 07 – K

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C07K 14/16 (2006.01) A61K 38/00 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2650485

The present invention relates to the use of a polyvalent synthetic compound comprising a support on which at least 3 pseudopeptide units are grafted, said compound being of formula (I), in which each X independently represents any amino acid; Y1 and Y2 are selected independently from amino acids having a basic side chain; Z is selected from a proline, optionally substituted at .noteq., - or ..; a natural or non-natural N-alkylamino acid; a dialkylamino acid; a cyclic dialkylamino acid; pipecolic acid or a derivative thereof; n and i independently are 0 or 1; m is an integer between 0 and 3; k is an integer greater than or equal to 3; and .PSI. represents a modified peptide bond which is significantly more resistant to at least one protease than a standard peptide bond, for preparing a medicament intended for treating a disease involving deregulation of cell proliferation and/or of angiogenesis, and preferably acting as a surface nucleolin ligand, or for treating inflammatory diseases.

La présente invention concerne l'utilisation d'un composé synthétique multivalent comprenant un support sur lequel sont greffés au moins 3 motifs pseudopeptidiques, ledit composé étant de formule (I), ou chaque X représente indépendamment un acide aminé quelconque ; Y1et Y2 sont indépendamment choisis parmi les acides aminés à chaîne latérale basique ; Z est choisi parmi une proline, éventuellement substituée en .noteq., - ou .. ; un acide aminé naturel ou non N-alkylé ; un acide aminé dialkylé ; un acide aminé dialkylé cyclique ; l'acide pipécolique ou l'un de ses dérivés ; n et i sont indépendamment 0 ou 1 ; m est un entier entre 0 et 3 ; k est un entier supérieur ou égal à 3 ; et .PSI. représente une liaison peptidique modifiée, significativement plus résistante à au moins une protéase qu'une liaison peptidique normale, pour la fabrication d'un médicament destiné au traitement d'une maladie impliquant une dérégulation de la prolifération cellulaire et/ou de l'angiogénèse, et de préférence agissant en tant que ligand de la nucléoline de surface, ou des maladies inflammatoires.

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