Complex Biophysical and Computational Analyses of G‐Quadruplex Ligands: The Porphyrin Stacks Back

Complex Biophysical and Computational Analyses of G‐Quadruplex Ligands: The Porphyrin Stacks Back

WoS Article

G-quadruplexes (G4 s), as non-canonical DNA structures, attracta great deal of research interest in the molecular biology as wellas in the material science fields. The use of small molecules asligands for G-quadruplexes has emerged as a tool to regulategene expression and telomeres maintenance. Meso-tetrakis-(N-methyl-4-pyridyl) porphyrin (TMPyP4) was shown as one of thefirst ligands for G-quadruplexes and it is still widely used. Wereport an investigation comprising molecular docking anddynamics, synthesis and multiple spectroscopic and spectro-metric determinations on simple cationic porphyrins and theirinteraction with different DNA sequences. This study enabledthe synthesis of tetracationic porphyrin derivatives that ex-hibited binding and stabilizing capacity against G-quadruplexstructures; the detailed characterization has shown that thepresence of amide groups at the periphery improves selectivityfor parallel G4 s binding over other structures. Taking intoaccount the ease of synthesis, 5,10,15,20-tetrakis-(1-acetamido-4-pyridyl) porphyrin bromide could be considered a betteralternative to TMPyP4 in studies involving G4 binding.

G-quadruplexes (G4 s), as non-canonical DNA structures, attracta great deal of research interest in the molecular biology as wellas in the material science fields. The use of small molecules asligands for G-quadruplexes has emerged as a tool to regulategene expression and telomeres maintenance. Meso-tetrakis-(N-methyl-4-pyridyl) porphyrin (TMPyP4) was shown as one of thefirst ligands for G-quadruplexes and it is still widely used. Wereport an investigation comprising molecular docking anddynamics, synthesis and multiple spectroscopic and spectro-metric determinations on simple cationic porphyrins and theirinteraction with different DNA sequences. This study enabledthe synthesis of tetracationic porphyrin derivatives that ex-hibited binding and stabilizing capacity against G-quadruplexstructures; the detailed characterization has shown that thepresence of amide groups at the periphery improves selectivityfor parallel G4 s binding over other structures. Taking intoaccount the ease of synthesis, 5,10,15,20-tetrakis-(1-acetamido-4-pyridyl) porphyrin bromide could be considered a betteralternative to TMPyP4 in studies involving G4 binding.

DNA, G-quadruplexes, Molecular dynamics, Molecular recognition, NMR

DNA, G-quadruplexes, Molecular dynamics, Molecular recognition, NMR

SATTA, G.; TRAJKOVSKI, M.; CANTARA, A.; MURA, M.; MELONI, C.; OLLA, G.; DOBROVOLNÁ, M.; PISANO, L.; GASPA, S.; SALIS, A.; DE LUCA, L.; MOCCI, F.; BRÁZDA, V.; PLAVEC, J.; CARRARO, M.

2025

18.09.2024

Wiley-VCH

0947-6539

CHEMISTRY-A EUROPEAN JOURNAL

30

69

Federal Republic of Germany

1

13

13

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202402600

http://hdl.handle.net/11012/250725

2024-Satta