Identification of drugs using complementary combinatorial...

C - Chemistry – Metallurgy – 07 – K

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C07K 1/04 (2006.01) C07K 14/47 (2006.01) G01N 33/53 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2270394

The present invention is directed to the identification of compounds in a compound library which can mediate the biological activity of a target receptor protein, even when the ligands which mediate that activity through binding to that receptor are not already known. The method comprises three steps: (1) Screen at least one potential surrogate combinatorial library for members (preferably peptides or nucleic acids) binding to the target protein (TP) and hence capable of use as surrogates for the unknown ligand in steps (2) and (3). (2) Screen at least one complementary library, preferably a combinatorial library (which is not limited to, and may not even include, peptides, or nucleic acids and hence is referred to on occasion as a "compound library"), for compounds which inhibit the binding of one or more surrogates from step (1) to TP, and, optionally, (3) determine whether the inhibitory compound mediates the biological activity of the said TP.

L'invention concerne l'identification de composés dans un bibliothèque de composés, qui peuvent être à l'origine de l'activité biologique d'une protéine réceptrice cible même lorsque les ligands à l'origine de l'activité par liaison à ce récepteur ne sont pas encore connus. Le procédé consiste: (1) à cribler au moins une bibliothèque combinatoire de substituts potentiels pour des éléments (de préférence des peptides ou des acides nucléiques) se liant à la protéine cible (PT) et donc pouvant être utilisés pour le ligand inconnu des étapes (2) et (3); (2) à cribler au moins une bibliothèque complémentaire, de préférence une bibliothèque combinatoire, (qui peut comporter, entre autres, des peptides ou des acides nucléiques et donc appelée parfois "bibliothèque de composés") pour des composés qui inhibent la liaison d'un ou plusieurs substituts de l'étape (1) de PT, et éventuellement (3) à déterminer si le composé inhibiteur est à l'origine ou non de l'activité biologique de ladite PT.

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