Aptamer inhibition of thrombus formation

A - Human Necessities – 61 – K

Patent

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Details

A61K 48/00 (2006.01) A61K 31/7088 (2006.01) A61K 38/36 (2006.01) A61P 7/02 (2006.01) C07H 21/00 (2006.01)

Patent

CA 2732809

Boronic acid-modified DNA-based aptamers can be selected to recognize fibrinogen through binding at a glycosy-lation site and thus are useful for probing the effect of glycosylation pattern changes on the ability for fibrinogen to mediate blood coagulation. In addition, the aptamers of the disclosure also have anticoagulation effects due to their binding to fibrinogen and its cleavage product fibrin. The present disclosure, therefore, encompasses methods for inhibiting fibrin coagulation with an aptamer capable of specifically binding to a glycosylation site of fibrinogen or fibrin. The disclosure further provides oligonucleotide ap-tamers comprising at least one nucleotide having a boronic acid thereon, where the aptamer is capable of selectively binding to a glycosylation site of fibrinogen, or the derivative thereof.

L'invention concerne des aptamères à base d'ADN modifié par acide boronique qui peuvent être sélectionnés pour reconnaître un fibrinogène par liaison au niveau d'un site de glycosylation, et qui sont ainsi utiles pour sonder l'effet de changement de modèle de glycosylation sur l'aptitude du fibrinogène à atténuer la coagulation sanguine. De plus, les aptamères de l'invention ont également des effets anticoagulation du fait de leur liaison au fibrinogène, et de la fibrine de produit de clivage. L'invention concerne par conséquent des procédés pour inhiber une coagulation de fibrine avec un aptamère capable de se lier spécifiquement à un site de glycosylation de fibrinogène ou fibrine. L'invention concerne en outre des aptamères oligonucléotidiques comprenant au moins un oligonucléotide ayant un acide boronique sur celui-ci, l'aptamère étant capable de se lier sélectivement à un site de glycosylation de fibrinogène, ou du dérivé de celui-ci.

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