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Dinuclear complex-induced DNA melting

Dinuclear copper complexes have been designed for molecular recognition in order to selectively bind to two neighboring phosphate moieties in the backbone of double strand DNA. Associated biophysical, biochemical and cytotoxic effects on DNA were investigated in previous works, where atomic force mi...

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Autores principales: Biere, Niklas, Kreft, Dennis, Walhorn, Volker, Schwarzbich, Sabrina, Glaser, Thorsten, Anselmetti, Dario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869567/
https://www.ncbi.nlm.nih.gov/pubmed/36691056
http://dx.doi.org/10.1186/s12951-023-01784-8
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author Biere, Niklas
Kreft, Dennis
Walhorn, Volker
Schwarzbich, Sabrina
Glaser, Thorsten
Anselmetti, Dario
author_facet Biere, Niklas
Kreft, Dennis
Walhorn, Volker
Schwarzbich, Sabrina
Glaser, Thorsten
Anselmetti, Dario
author_sort Biere, Niklas
collection PubMed
description Dinuclear copper complexes have been designed for molecular recognition in order to selectively bind to two neighboring phosphate moieties in the backbone of double strand DNA. Associated biophysical, biochemical and cytotoxic effects on DNA were investigated in previous works, where atomic force microscopy (AFM) in ambient conditions turned out to be a particular valuable asset, since the complexes influence the macromechanical properties and configurations of the strands. To investigate and scrutinize these effects in more depth from a structural point of view, cutting-edge preparation methods and scanning force microscopy under ultra-high vacuum (UHV) conditions were employed to yield submolecular resolution images. DNA strand mechanics and interactions could be resolved on the single base pair level, including the amplified formation of melting bubbles. Even the interaction of singular complex molecules could be observed. To better assess the results, the appearance of treated DNA is also compared to the behavior of untreated DNA in UHV on different substrates. Finally, we present data from a statistical simulation reasoning about the nanomechanics of strand dissociation. This sort of quantitative experimental insights paralleled by statistical simulations impressively shade light on the rationale for strand dissociations of this novel DNA interaction process, that is an important nanomechanistic key and novel approach for the development of new chemotherapeutic agents. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-01784-8.
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spelling pubmed-98695672023-01-24 Dinuclear complex-induced DNA melting Biere, Niklas Kreft, Dennis Walhorn, Volker Schwarzbich, Sabrina Glaser, Thorsten Anselmetti, Dario J Nanobiotechnology Research Dinuclear copper complexes have been designed for molecular recognition in order to selectively bind to two neighboring phosphate moieties in the backbone of double strand DNA. Associated biophysical, biochemical and cytotoxic effects on DNA were investigated in previous works, where atomic force microscopy (AFM) in ambient conditions turned out to be a particular valuable asset, since the complexes influence the macromechanical properties and configurations of the strands. To investigate and scrutinize these effects in more depth from a structural point of view, cutting-edge preparation methods and scanning force microscopy under ultra-high vacuum (UHV) conditions were employed to yield submolecular resolution images. DNA strand mechanics and interactions could be resolved on the single base pair level, including the amplified formation of melting bubbles. Even the interaction of singular complex molecules could be observed. To better assess the results, the appearance of treated DNA is also compared to the behavior of untreated DNA in UHV on different substrates. Finally, we present data from a statistical simulation reasoning about the nanomechanics of strand dissociation. This sort of quantitative experimental insights paralleled by statistical simulations impressively shade light on the rationale for strand dissociations of this novel DNA interaction process, that is an important nanomechanistic key and novel approach for the development of new chemotherapeutic agents. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-01784-8. BioMed Central 2023-01-23 /pmc/articles/PMC9869567/ /pubmed/36691056 http://dx.doi.org/10.1186/s12951-023-01784-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Biere, Niklas
Kreft, Dennis
Walhorn, Volker
Schwarzbich, Sabrina
Glaser, Thorsten
Anselmetti, Dario
Dinuclear complex-induced DNA melting
title Dinuclear complex-induced DNA melting
title_full Dinuclear complex-induced DNA melting
title_fullStr Dinuclear complex-induced DNA melting
title_full_unstemmed Dinuclear complex-induced DNA melting
title_short Dinuclear complex-induced DNA melting
title_sort dinuclear complex-induced dna melting
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869567/
https://www.ncbi.nlm.nih.gov/pubmed/36691056
http://dx.doi.org/10.1186/s12951-023-01784-8
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