Telomeric G-quadruplexes (G4s) are promising targets in the design and development of anticancer drugs. Their actual topology depends on several factors, resulting in structural polymorphism. In this study, we investigate how the fast dynamics of the telomeric sequence AG (Formula presented.) (TTAG (Formula presented.)) (Formula presented.) (Tel22) depends on the conformation. By using Fourier transform Infrared spectroscopy, we show that, in the hydrated powder state, Tel22 adopts parallel and mixed antiparallel/parallel topologies in the presence of K (Formula presented.) and Na (Formula presented.) ions, respectively. These conformational differences are reflected in the reduced mobility of Tel22 in Na (Formula presented.) environment in the sub-nanosecond timescale, as probed by elastic incoherent neutron scattering. These findings are consistent with the G4 antiparallel conformation being more stable than the parallel one, possibly due to the presence of ordered hydration water networks. In addition, we study the effect of Tel22 complexation with BRACO19 ligand. Despite the quite similar conformation in the complexed and uncomplexed state, the fast dynamics of Tel22-BRACO19 is enhanced compared to that of Tel22 alone, independently of the ions. We ascribe this effect to the preferential binding of water molecules to Tel22 against the ligand. The present results suggest that the effect of polymorphism and complexation on the G4 fast dynamics is mediated by hydration water.
Polymorphism and Ligand Binding Modulate Fast Dynamics of Human Telomeric G-Quadruplexes / Bertini, L.; Libera, V.; Ripanti, F.; Natali, F.; Paolantoni, M.; Orecchini, A.; Nucara, A.; Petrillo, C.; Comez, L.; Paciaroni, A.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 24:5(2023). [10.3390/ijms24054280]
Polymorphism and Ligand Binding Modulate Fast Dynamics of Human Telomeric G-Quadruplexes
Ripanti F.
;
2023-01-01
Abstract
Telomeric G-quadruplexes (G4s) are promising targets in the design and development of anticancer drugs. Their actual topology depends on several factors, resulting in structural polymorphism. In this study, we investigate how the fast dynamics of the telomeric sequence AG (Formula presented.) (TTAG (Formula presented.)) (Formula presented.) (Tel22) depends on the conformation. By using Fourier transform Infrared spectroscopy, we show that, in the hydrated powder state, Tel22 adopts parallel and mixed antiparallel/parallel topologies in the presence of K (Formula presented.) and Na (Formula presented.) ions, respectively. These conformational differences are reflected in the reduced mobility of Tel22 in Na (Formula presented.) environment in the sub-nanosecond timescale, as probed by elastic incoherent neutron scattering. These findings are consistent with the G4 antiparallel conformation being more stable than the parallel one, possibly due to the presence of ordered hydration water networks. In addition, we study the effect of Tel22 complexation with BRACO19 ligand. Despite the quite similar conformation in the complexed and uncomplexed state, the fast dynamics of Tel22-BRACO19 is enhanced compared to that of Tel22 alone, independently of the ions. We ascribe this effect to the preferential binding of water molecules to Tel22 against the ligand. The present results suggest that the effect of polymorphism and complexation on the G4 fast dynamics is mediated by hydration water.File | Dimensione | Formato | |
---|---|---|---|
2023_Luca-IONS_IJMS.pdf
accesso aperto
Descrizione: versione editoriale
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza d'uso:
Creative commons
Dimensione
1.96 MB
Formato
Adobe PDF
|
1.96 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.