Synthesis of Porphyrins for the Development of Inhibitors and Sensors for Biomedical Applications

Guanine-rich sequences with at least 3 consecutive residues can fold to form non-canonical quaternary structures. Pairing of 4 guanines forms G-tetrads which, when stacked, form G-quadruplexes (G4) which are stabilised by metal cations naturally present in the cellular environment, such as sodium or potassium. G4 are relevant to many biologi-cal processes because guanine-rich sequences are found in telomeres, oncogene promoters, replication start sites and untranslated regions of the human genome. Some studies have linked them to potential anticancer therapies, such as telomerase inhibition or transcrip-tional modification of c-Myc. In fact, the presence of these structures acts as a physical block by preventing the unfolding of the gene sequences. The coordinating and stabilising capacity of some novel tetra cationic porphyrin ligands towards G4 has been investigated in this work. After assessing their ligand properties by molecular dynamics studies, a structural study of the complexes was carried out using spectroscopic techniques such as nuclear magnetic resonance and circular dichroism. The selectivity of these ligands for G4 with parallel topology was highlighted and analyses were also carried out under molecular crowding conditions. In addition, the stabilisation behaviour was evaluated by mass spec-trometry studies. Preliminary biological tests showed the in vitro activity of the proposed ligands.