Study of MDM2 binding site with the p-53 and its interaction with disruptive molecules

CINTIA A. MENÉNDEZ; SEBASTIÁN R. ACCORDINO; GUSTAVO A. APPIGNANESI; DARÍO C. GERBINO

Caxambu

Congreso; XXXIX Congress of Brazilian Biophysical Society; 2014

Sociedad Brasileña de Biofísica

The object of study of this work is the binding site of MDM2 protein with tumor suppressor p53, as well as the interaction between MDM2 with nutlin as disruptive molecules and different xanthones, focusing our interest in principle in the 3,4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3,2-b]xanthen-6-one. The latter are part of a novel family of oxygenated heterocycles, found in nature in various species of fungi, algae and higher plants. The study of such compounds is of great interest because they possess interesting biological activities with potential therapeutic applications. Using molecular dynamics studies was possible to establish which are presumably three fundamental positions in the binding site of MDM2 is necessary "to cover." In these positions the natural "partner" (p53) accommodates hydrophobic residues, behavior that is mimicked by nutlin. The xanthone studied also binds to the same site or "hot spot", but only has the ability to cover two of these positions simultaneously, reason that adopts different conformations along time, alternating their interaction with those positions. From these results it would be possible to rationally functionalize this prototype and achieve an increase in its activity as an inhibitor of the MDM2-p53 interaction.