Approches pour l'inhibition de l'aldolase FBP de classe II
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L'aldolase du fructose-1,6-bisphosphate (FBP) (E.C. 4.1.2.13) catalyse la condensation aldolique r�versible du dihydroxyac�tonephosphate (DHAP) et du glyc�rald�hyde-3-phosphate (G3P) dans la glycolyse, la glucon�ogen�se et le cycle de Calvin. Les aldolases FBP sont class�es en deux groupes en fonction de leurs m�canismes catalytiques diff�rents. Il convient de noter que l'aldolase de classe II n'existe ni chez les animaux ni chez les plantes, ce qui fait de cette enzyme une cible th�rapeutique potentielle pour les micro-organismes pathog�nes tels que Mycobacterium tuberculosis. Un substrat chromog�ne a �t� synth�tis� pour imiter le FBP. Ce substrat chromog�ne peut �tre utilis� dans un test chromog�ne direct pour surveiller l'activit� des aldolases FBP de classe II et pour �valuer tout inhibiteur efficace. De plus, notre groupe de recherche a d�couvert qu'un antidote disponible dans le commerce contre l'intoxication aux m�taux lourds, l'acide 2,3-dimercapto-1-propanesulfonique (DMPS), est un bon inhibiteur comp�titif de l'aldolase FBP de classe II. Afin d'am�liorer l'affinit� de liaison de cet inhibiteur au site actif de l'enzyme, de nouvelles mol�cules bas�es sur ce compos� ont �t� con�ues de mani�re rationnelle � l'aide de la mod�lisation mol�culaire.
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