Tácticas químicas para controlar a interacción de sistemas sintéticos con ácidos nucleicos

Abstract

This thesis reports the design and synthesis of three different systems able to interact and recognize specific sequences of nucleic acids. In the first part, functional analogues of the oncoprotein MYC and its negative dominant OMOMYC, as well as fluorescently labelled derivatives, were synthesized in very good yields using two alternative strategies which involve either one or two Native Chemical Ligations. These therapeutically relevant miniproteins are able to dimerize and recognize the major groove of the E-DNA and successful internalize living cells. The second part describes the synthesis of switchable systems capable of interacting specifically with the minor groove of A/T-rich sequences of DNA in a reversible and externally controllable manner. In the last chapter, fluorescent bisbenzamidine oligomers were obtained in one pot which showed remarkably very high affinities for different A/T base pair combinations of dsDNA by inserting in the minor groove.