Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Musetti, Caterina, Krapcho, A. Paul, Palumbo, Manlio, Sissi, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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
_version_ 1782262489488031744
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
work_keys_str_mv AT musetticaterina effectofgquadruplexpolymorphismontherecognitionoftelomericdnabyametalcomplex
AT krapchoapaul effectofgquadruplexpolymorphismontherecognitionoftelomericdnabyametalcomplex
AT palumbomanlio effectofgquadruplexpolymorphismontherecognitionoftelomericdnabyametalcomplex
AT sissiclaudia effectofgquadruplexpolymorphismontherecognitionoftelomericdnabyametalcomplex