Targeting G-quadruplexes with organic dyes: Chelerythrine–DNA binding elucidated by combining molecular modeling and optical spectroscopy

Alessio Terenzi, Angelo Spinello, Giampaolo Barone, Antonio Monari, Alessio Terenzi, Bernhard K. Keppler, Angelo Spinello, Hugo Gattuso, François Dehez, Christophe Chipot

Risultato della ricerca: Articlepeer review

2 Citazioni (Scopus)

Abstract

The DNA-binding of the natural benzophenanthridine alkaloid chelerythrine (CHE) has been assessed by combining molecular modeling and optical absorption spectroscopy. Specifically, both double-helical (B-DNA) and G-quadruplex sequences—representative of different topologies and possessing biological relevance, such as telomeric or regulatory sequences—have been considered. An original multiscale protocol, making use of molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations, allowed us to compare the theoretical and experimental circular dichroism spectra of the different DNA topologies, readily providing atomic-level details of the CHE–DNA binding modes. The binding selectivity towards G-quadruplexes is confirmed by both experimental and theoretical determination of the binding free energies. Overall, our mixed computational and experimental approach is able to shed light on the interaction of small molecules with different DNA conformations. In particular, CHE may be seen as the building block of promising drug candidates specifically targeting G-quadruplexes for both antitumoral and antiviral purposes.
Lingua originaleEnglish
pagine (da-a)1-15
Numero di pagine15
RivistaAntioxidants
Volume8
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry
  • Physiology
  • Molecular Biology

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