Naslov
Thermodynamic fingerprints of ligand binding to human telomeric G-quadruplexes

Autori
Bončina, Matjaž ; Podlipnik, Črtomir ; Piantanida, Ivo ; Eilmes, Julita ; Teulade-Fichou, Marie-Paule ; Vesnaver, Gorazd ; Lah, Jurij

Izvornik
Nucleic acids research (0305-1048) 43 (2015), 21; 10376-10386

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
G-quadruplex; thermodynamic recognition; ligand binding; ITC; CD; fluorimetry

Sažetak
Thermodynamic studies of ligand binding to human telomere (ht) DNA quadruplexes, as a rule, neglect the involvement of various ht-DNA conformations in the binding process. Therefore, the thermodynamic driving forces and the mechanisms of ht-DNA G-quadruplex-ligand recognition remain poorly understood. In this work we characterize thermodynamically and structurally binding of netropsin (Net), dibenzotetraaza[14]annulene derivatives (DP77, DP78), cationic porphyrin (TMPyP4) and two bisquinolinium ligands (Phen-DC3, 360A-Br) to the ht-DNA fragment (Tel22) AGGG(TTAGGG)3 using isothermal titration calorimetry, CD and fluorescence spectroscopy, gel electrophoresis and molecular modeling. By global thermodynamic analysis of experimental data we show that the driving forces characterized by contributions of specific interactions, changes in solvation and conformation differ significantly for binding of ligands with low quadruplex selectivity over duplexes (Net, DP77, DP78, TMPyP4 ; KTel22 < KdsDNA) and for highly selective quadruplex-specific ligands (Phen-DC3, 360A-Br ; KTel22 > KdsDNA). These contributions are in accordance with the observed structural features (changes) and suggest that upon binding Net, DP77, DP78 and TMPyP4 select the hybrid Tel22 conformation while Phen-DC3 and 360A-Br induce the transition from the hybrid to the distorted antiparallel Tel22 conformation.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA