G-quadruplexes: design, synthesis and characterization of new modified ODNs and natural ligands.

Abstract

PhD project is focused on the synthesis and biophysically and biologically characterization of a new mini-library of d(TGGGAG) oligomers as potential anti-HIV. It has been developed an efficient procedure to synthesize modified d(TGGGAG) oligomers carrying hydrophobic and aromatic groups at the 5'-end by a phosphodiester bond. In addition, aiming at improving the kinetic of G-quadruplex formation using d(TGGGAG) as a lead sequence, it have been synthesized bimolecular G-quadruplexes based on d(TGGGAG) sequence containing a HEG loop as a 3'-3' or 5'-5' inversion of polarity site. Kinetic studies of G-quadruplex formation based on the most active 5'-end modified d(TGGGAG) sequences are carried out using ESI-Mass Spectrometry. The interest in G-quadruplex structures has greatly expanded for their existence in vivo in several important oncogenes and in human telomeres. Many antitumor strategies have been developed on the inhibition of telomerase activity through the use of specific ligands. In this frame, it has been analysed the potentiality of a natural compound, namely silibinin. It has been performed an efficient HPLC preparative method to obtain the pure form of silibinin (silybin A and B), and it has been developed a base-catalyzed oxidation of silybin A and B by microwave (MW), which leads to biologically interesting product: the 2,3-dehydrosilybin A and B.