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Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex
The physiological role(s) played by G-quadruplexes renders these ‘non-canonical’ DNA secondary structures interesting new targets for therapeutic intervention. In particular, the search for ligands for selective recognition and stabilization of G-quadruplex arrangements has led to a number of novel...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596309/ https://www.ncbi.nlm.nih.gov/pubmed/23516498 http://dx.doi.org/10.1371/journal.pone.0058529 |
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author | Musetti, Caterina Krapcho, A. Paul Palumbo, Manlio Sissi, Claudia |
author_facet | Musetti, Caterina Krapcho, A. Paul Palumbo, Manlio Sissi, Claudia |
author_sort | Musetti, Caterina |
collection | PubMed |
description | The physiological role(s) played by G-quadruplexes renders these ‘non-canonical’ DNA secondary structures interesting new targets for therapeutic intervention. In particular, the search for ligands for selective recognition and stabilization of G-quadruplex arrangements has led to a number of novel targeted agents. An interesting approach is represented by the use of metal-complexes, their binding to DNA being modulated by ligand and metal ion nature, and by complex stoichiometry. In this work we characterized thermodynamically and stereochemically the interactions of a Ni(II) bis-phenanthroline derivative with telomeric G-quadruplex sequences using calorimetric, chiroptical and NMR techniques. We employed three strictly related sequences based on the human telomeric repeat, namely Tel22, Tel26 and wtTel26, which assume distinct conformations in potassium containing solutions. We were able to monitor specific enthalpy/entropy changes according to the structural features of the target telomeric sequence and to dissect the binding process into distinct events. Interestingly, temperature effects turned out to be prominent both in terms of binding stoichiometry and ΔH/ΔS contributions, while the final G-quadruplex-metal complex architecture tended to merge for the examined sequences. These results underline the critical choice of experimental conditions and DNA sequence for practical use of thermodynamic data in the rational development of effective G-quadruplex binders. |
format | Online Article Text |
id | pubmed-3596309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35963092013-03-20 Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex Musetti, Caterina Krapcho, A. Paul Palumbo, Manlio Sissi, Claudia PLoS One Research Article The physiological role(s) played by G-quadruplexes renders these ‘non-canonical’ DNA secondary structures interesting new targets for therapeutic intervention. In particular, the search for ligands for selective recognition and stabilization of G-quadruplex arrangements has led to a number of novel targeted agents. An interesting approach is represented by the use of metal-complexes, their binding to DNA being modulated by ligand and metal ion nature, and by complex stoichiometry. In this work we characterized thermodynamically and stereochemically the interactions of a Ni(II) bis-phenanthroline derivative with telomeric G-quadruplex sequences using calorimetric, chiroptical and NMR techniques. We employed three strictly related sequences based on the human telomeric repeat, namely Tel22, Tel26 and wtTel26, which assume distinct conformations in potassium containing solutions. We were able to monitor specific enthalpy/entropy changes according to the structural features of the target telomeric sequence and to dissect the binding process into distinct events. Interestingly, temperature effects turned out to be prominent both in terms of binding stoichiometry and ΔH/ΔS contributions, while the final G-quadruplex-metal complex architecture tended to merge for the examined sequences. These results underline the critical choice of experimental conditions and DNA sequence for practical use of thermodynamic data in the rational development of effective G-quadruplex binders. Public Library of Science 2013-03-13 /pmc/articles/PMC3596309/ /pubmed/23516498 http://dx.doi.org/10.1371/journal.pone.0058529 Text en © 2013 Musetti et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Musetti, Caterina Krapcho, A. Paul Palumbo, Manlio Sissi, Claudia Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex |
title | Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex |
title_full | Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex |
title_fullStr | Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex |
title_full_unstemmed | Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex |
title_short | Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex |
title_sort | effect of g-quadruplex polymorphism on the recognition of telomeric dna by a metal complex |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596309/ https://www.ncbi.nlm.nih.gov/pubmed/23516498 http://dx.doi.org/10.1371/journal.pone.0058529 |
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