The Binding Pocket at the Interface of Multimeric Telomere G-quadruplexes: Myth or Reality?
Fluorescence Lifetime and Multiwavelength Global Analysis
Human Telomeric DNA
Isothermal Titration Calorimetry
Multimeric G-quadruplexes
Naphthalene diimide dyads
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783
Informations de publication
Date de publication:
11 Aug 2021
11 Aug 2021
Historique:
received:
26
04
2021
pubmed:
22
6
2021
medline:
18
8
2021
entrez:
21
6
2021
Statut:
ppublish
Résumé
Human telomeric DNA with hundreds of repeats of the 5'-TTAGGG-3' motif plays a crucial role in several biological processes. It folds into G-quadruplex (G4) structures and features a pocket at the interface of two contiguous G4 blocks. Up to now no structural NMR and crystallographic data are available for ligands interacting with contiguous G4s. Naphthalene diimide monomers and dyads were investigated as ligands of a dimeric G4 of human telomeric DNA comparing the results with those of the model monomeric G4. Time-resolved fluorescence, circular dichroism, isothermal titration calorimetry and molecular modeling were used to elucidate binding features. Ligand fluorescence lifetime and induced circular dichroism unveiled occupancy of the binding site at the interface. Thermodynamic parameters confirmed the hypothesis as they remarkably change for the dyad complexes of the monomeric and dimeric telomeric G4. The bi-functional ligand structure of the dyads is a fundamental requisite for binding at the G4 interface as only the dyads engage in complexes with 1 : 1 stoichiometry, lodging in the pocket at the interface and establishing multiple interactions with the DNA skeleton. In the absence of NMR and crystallographic data, our study affords important proofs of binding at the interface pocket and clues on the role played by the ligand structure.
Identifiants
pubmed: 34152657
doi: 10.1002/chem.202101486
pmc: PMC8456957
doi:
Substances chimiques
Ligands
0
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11707-11720Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG 14708
Informations de copyright
© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.
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