Method of screening compound regulating the translation of...

C - Chemistry – Metallurgy – 07 – H

Patent

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C07H 21/02 (2006.01) A61K 31/00 (2006.01) C12N 1/15 (2006.01) C12N 1/19 (2006.01) C12N 1/21 (2006.01) C12N 5/10 (2006.01) C12N 15/00 (2006.01) C12N 15/09 (2006.01) C12Q 1/68 (2006.01) G06F 19/00 (2006.01)

Patent

CA 2587719

It is intended to provide a method of screening a compound, by which a specific disease can be prevented or treated, comprising: (1) the step of selecting one or more mRNAs the regulation of the translation of which enables the prevention or treatment of the disease; (2) the step of searching for an mRNA having a sequence capable of undergoing a local secondary structure allowing the regulation of the translation of the mRNA in its molecule from among the mRNAs selected in the above step (1); (3) the step of selecting a specific sequence from the sequences capable of undergoing a local secondary structure in the specific mRNA extracted in the above step (2); (4) the step of confirming whether or not the partial structure capable of interacting with a compound in the specific sequence selected in the above step (3) occurring in a region relating to the regulation of the translation of other mRNAs or, if occurring, being incapable of regulating the translation; and (5) the step of contacting an RNA chain containing the specific sequence that has been confirmed as not occurring in a region relating to the regulation of the translation of other mRNAs in the above step (4) with a test compound and then measuring a change in the stability of the secondary structure of this RNA chain.

L~invention concerne un procédé permettant de cribler un composé pour prévenir ou traiter une maladie spécifique, procédé comprenant les phases suivantes : (1) sélection d~un ou de plusieurs ARNm, dont la régulation de la traduction permet la prévention ou le traitement de la maladie ; (2) recherche d~un ARNm ayant une séquence capable de subir une structure secondaire locale permettant la régulation de la traduction de l~ARNm dans sa molécule parmi les ARNm sélectionnés lors de la phase précédente (1) ; (3) sélection d~une séquence spécifique parmi les séquences capables de subir une structure secondaire locale dans l~ARNm spécifique extrait dans la phase ci-dessus (2); (4) confirmation que la structure partielle capable d~interagir avec un composé de la séquence spécifique sélectionnée lors de la phase ci-dessus (3) se manifeste ou non dans une région se rapportant à la régulation de la traduction d~autres ARNm ou, si manifestation il y a, qu~elle est incapable de réguler la traduction ; et (5) mise en contact d~une chaîne ARN contenant la séquence spécifique ayant été confirmée comme ne se manifestant pas dans une région se rapportant à la régulation de la traduction d~autres ARNm dans la phase ci-dessus (4) avec un composé d~essai, puis mesure d~un changement de stabilité de la structure secondaire de cette chaîne ARN.

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