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The Binding Pocket at the Interface of Multimeric Telomere G-quadruplexes: Myth or Reality?
- Source :
- Chemistry (Weinh., Print) 27 (2021): 11707–11720. doi:10.1002/chem.202101486, info:cnr-pdr/source/autori:Manoli, Francesco; Doria, Filippo; Colombo, Giorgio; Zambelli, Barbara; Freccero, Mauro; Manet, Ilse/titolo:The Binding Pocket at the Interface of Multimeric Telomere G-quadruplexes: Myth or Reality?/doi:10.1002%2Fchem.202101486/rivista:Chemistry (Weinh., Print)/anno:2021/pagina_da:11707/pagina_a:11720/intervallo_pagine:11707–11720/volume:27, Chemistry (Weinheim an Der Bergstrasse, Germany)
- Publication Year :
- 2021
-
Abstract
- 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.<br />Binding of naphthalenediimide (NDI) dyads at the interface of contiguous telomeric G‐quadruplexes (G4) in hTel45 is revealed by synergically combining time‐resolved fluorescence, induced circular dichroism and isothermal titration calorimetry and further rationalized with modeling data. In the absence of NMR and crystallographic data the approach used afforded new information that can help to rationalize the biological behavior of these ligands.
- Subjects :
- Multimeric G-quadruplexe
Circular dichroism
Isothermal Titration Calorimetry
Molecular model
Ligand
G-quadruplex
Ligands
Catalysis
chemistry.chemical_compound
Human Telomeric DNA
Humans
Binding site
Fluorescence Lifetime and Multiwavelength Global Analysi
Full Paper
Fluorescence Lifetime and Multiwavelength Global Analysis
Naphthalene diimide dyad
Circular Dichroism
Organic Chemistry
Isothermal titration calorimetry
General Chemistry
DNA
Full Papers
Telomere
Multimeric G-quadruplexes
Naphthalene diimide dyads
G-Quadruplexes
Crystallography
Monomer
chemistry
Human
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Chemistry (Weinh., Print) 27 (2021): 11707–11720. doi:10.1002/chem.202101486, info:cnr-pdr/source/autori:Manoli, Francesco; Doria, Filippo; Colombo, Giorgio; Zambelli, Barbara; Freccero, Mauro; Manet, Ilse/titolo:The Binding Pocket at the Interface of Multimeric Telomere G-quadruplexes: Myth or Reality?/doi:10.1002%2Fchem.202101486/rivista:Chemistry (Weinh., Print)/anno:2021/pagina_da:11707/pagina_a:11720/intervallo_pagine:11707–11720/volume:27, Chemistry (Weinheim an Der Bergstrasse, Germany)
- Accession number :
- edsair.doi.dedup.....1aada1de084a0a534794f597c8803fd5