Modulators of dna cytosine-5 methyltransferase and methods...

C - Chemistry – Metallurgy – 12 – N

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Details

C12N 15/54 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) C07H 21/00 (2006.01) C12N 15/10 (2006.01) C12N 15/11 (2006.01) C12Q 1/48 (2006.01) C12Q 1/68 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2300354

A synthetic oligonucleotide comprising a C-5 methylcytosine and which recognizes and binds an allosteric site on DNA methyltransferase thereby inhibiting DNA methyltransferase activity is disclosed. Also disclosed is a composition comprising a synthetic oligonucleotide of the invention. The composition is useful for inhibiting DNA methyltransferase activity, thereby inhibiting the methylation of DNA. The composition can be a pharmaceutical composition useful for treating disorders associated with methylation defects, such as cancer and certain developmental disorders. Also disclosed is a method of inhibiting methylation of DNA. The method involves contacting a DCMTase with a synthetic oligonucleotide of the invention in the presence of the DNA, thereby resulting in an enzyme/synthetic oligonucleotide complex. The presence of the complex prevents catalysis, thereby inhibiting DNA methyltransferase activity. Also disclosed is a method of treating a disorder of cell proliferation or development by administering to a subject a synthetic oligonucleotide of the invention. The inhibition of DNA methyltransferase prevents the methylation of DNA thereby treating the disorder of cell proliferation or development.

L'invention concerne un oligonucléotide synthétique qui comprend un méthylcytosine C-5 et qui reconnaît et lie un site allostérique sur ADN méthyltransférase, ce qui freine l'activité d'ADN méthyltransférase. L'invention concerne également une composition comprenant un oligonucléotide synthétique de la présente invention. La composition peut servir à freiner l'activité d'ADN méthyltransférase et, par conséquent, à inhiber la méthylation d'ADN. Cette composition peut se présenter comme une composition pharmaceutique utilisée pour traiter des troubles, liés aux défauts de méthylation, tels que le cancer et certaines anomalies du développement. L'invention concerne aussi un procédé pour inhiber la méthylation de l'ADN. Le procédé consiste à mettre en contact une DCMTase et un oligonucléotide synthétique de cette invention, en présence de l'ADN, pour obtenir un complexe enzyme / oligonucléotide synthétique. La présence de ce complexe empêche la catalyse et freine ainsi l'activité d'ADN méthyltransférase. En outre, l'invention concerne un procédé qui sert à traiter l'anomalie de prolifération ou de développement cellulaires et qui consiste à administrer à un sujet un oligonucléotide synthétique de cette invention. L'inhibition d'ADN méthyltransférase empêche la méthylation d'ADN, ce qui permet de traiter l'anomalie de prolifération ou de développement cellulaires.

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