Generation of combinatorial libraries and assessment thereof...

C - Chemistry – Metallurgy – 07 – B

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C07B 61/00 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2421197

The present invention deals with a method for the generation of a dynamic combinatorial library of ligands for a given target, capable of binding at least two functionalities, which method comprises the following steps: (i) selecting a set of n molecules carrying functionalities which may bind to the target, which molecules are capable of reversibly binding to each other under formation of an entity, n being an integer >= 1; (ii) mixing together said set of said n molecules; (iii) subjecting the mixture to conditions allowing a reversible bond formation and cleavage under formation of entities carrying different combinations of functionalities, until equilibrium is reached; (iv) optionally transforming the said entities into ligands; (v) repeating steps (i) to (iv) n-times, each time a different molecule of said set of n molecules being omitted; (vi) assessing the ability of each of the mixtures obtained to bind to a given target.

La présente invention concerne un procédé permettant de générer une banque combinatoire dynamique de ligands pour une cible donnée pouvant relier au moins deux fonctionnalités. Ce procédé englobe les étapes suivantes : (i) sélection d'un ensemble de n molécules portant des fonctionnalités qui peuvent être reliées à la cible, lesdites molécules étant capables de se lier de manière réversible les unes aux autres pour former une entité, n étant un entier >= 1; (ii) mélanger ledit ensemble de n molécules; (iii) soumettre le mélange à des conditions qui autorisent la formation d'une liaison réversible et le clivage par formation d'entités portant des combinaisons différentes de fonctionnalités jusqu'à ce qu'un équilibre soit atteint; (iv) éventuellement, transformation desdites entités en ligands; (v) répétition des opérations (i) à (iv) n fois, en omettant chaque fois une molécule différente dudit ensemble de n molécules; (vi) évaluation de l'aptitude de chacun des mélanges obtenus à se lier à une cible donnée.

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