G-quadruplexes (G4 s), as non-canonical DNA structures, attract a great deal of research interest in the molecular biology as well as in the material science fields. The use of small molecules as ligands for G-quadruplexes has emerged as a tool to regulate gene expression and telomeres maintenance. Meso-tetrakis-(N-methyl-4-pyridyl) porphyrin (TMPyP4) was shown as one of the first ligands for G-quadruplexes and it is still widely used. We report an investigation comprising molecular docking and dynamics, synthesis and multiple spectroscopic and spectrometric determinations on simple cationic porphyrins and their interaction with different DNA sequences. This study enabled the synthesis of tetracationic porphyrin derivatives that exhibited binding and stabilizing capacity against G-quadruplex structures; the detailed characterization has shown that the presence of amide groups at the periphery improves selectivity for parallel G4 s binding over other structures. Taking into account the ease of synthesis, 5,10,15,20-tetrakis-(1-acetamido-4-pyridyl) porphyrin bromide could be considered a better alternative to TMPyP4 in studies involving G4 binding.

Consorzio Interuniversitario Reattività Chimica e Catalisi Via Celso Ulpiani 27 Bari 70126 Italy

Department of Chemical Physical Mathematical and Natural Sciences University of Sassari Via Vienna 2 Sassari 07100 Italy

Department of Chemistry and Geological Science University of Cagliari Cittadella Universitaria 1 09042 Monserrato Italy

EN→FIST Centre of Excellence Trg OF 13 SI 1000 Ljubljana Slovenia

Faculty of Chemistry and Chemical Technology University of Ljubljana Vecna pot 113 SI 1000 Ljubljana Slovenia

Institute of Biophysics Czech Academy of Sciences Královopolská 135 612 65 Brno Czech Republic

Slovenian NMR Centre National Institute of Chemistry Ljubljana SI 1000 Slovenia

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