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Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates

The design of molecules that damage a selected DNA sequence provides a formidable opportunity for basic and applied biology. For example, such molecules offer new prospects for controlled manipulation of the genome. The conjugation of DNA-code reading molecules such as polyamides to reagents that in...

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Autores principales: Simon, Philippe, Cannata, Fabio, Perrouault, Loïc, Halby, Ludovic, Concordet, Jean-Paul, Boutorine, Alexandre, Ryabinin, Vladimir, Sinyakov, Alexandre, Giovannangeli, Carine
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441794/
https://www.ncbi.nlm.nih.gov/pubmed/18450816
http://dx.doi.org/10.1093/nar/gkn231
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author Simon, Philippe
Cannata, Fabio
Perrouault, Loïc
Halby, Ludovic
Concordet, Jean-Paul
Boutorine, Alexandre
Ryabinin, Vladimir
Sinyakov, Alexandre
Giovannangeli, Carine
author_facet Simon, Philippe
Cannata, Fabio
Perrouault, Loïc
Halby, Ludovic
Concordet, Jean-Paul
Boutorine, Alexandre
Ryabinin, Vladimir
Sinyakov, Alexandre
Giovannangeli, Carine
author_sort Simon, Philippe
collection PubMed
description The design of molecules that damage a selected DNA sequence provides a formidable opportunity for basic and applied biology. For example, such molecules offer new prospects for controlled manipulation of the genome. The conjugation of DNA-code reading molecules such as polyamides to reagents that induce DNA damages provides an approach to reach this goal. In this work, we showed that a bipyridine conjugate of polyamides was able to induce sequence-specific DNA breaks in cells. We synthesized compounds based on two polyamide parts linked to bipyridine at different positions. Bipyridine conjugates of polyamides were found to have a high affinity for the DNA target and one of them produced a specific and high-yield cleavage in vitro and in cultured cells. The bipyridine conjugate studied here, also presents cell penetrating properties since it is active when directly added to cell culture medium. Harnessing DNA damaging molecules such as bipyridine to predetermined genomic sites, as achieved here, provides an attractive strategy for targeted genome modification and DNA repair studies.
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spelling pubmed-24417942008-07-02 Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates Simon, Philippe Cannata, Fabio Perrouault, Loïc Halby, Ludovic Concordet, Jean-Paul Boutorine, Alexandre Ryabinin, Vladimir Sinyakov, Alexandre Giovannangeli, Carine Nucleic Acids Res Molecular Biology The design of molecules that damage a selected DNA sequence provides a formidable opportunity for basic and applied biology. For example, such molecules offer new prospects for controlled manipulation of the genome. The conjugation of DNA-code reading molecules such as polyamides to reagents that induce DNA damages provides an approach to reach this goal. In this work, we showed that a bipyridine conjugate of polyamides was able to induce sequence-specific DNA breaks in cells. We synthesized compounds based on two polyamide parts linked to bipyridine at different positions. Bipyridine conjugates of polyamides were found to have a high affinity for the DNA target and one of them produced a specific and high-yield cleavage in vitro and in cultured cells. The bipyridine conjugate studied here, also presents cell penetrating properties since it is active when directly added to cell culture medium. Harnessing DNA damaging molecules such as bipyridine to predetermined genomic sites, as achieved here, provides an attractive strategy for targeted genome modification and DNA repair studies. Oxford University Press 2008-06 2008-05-01 /pmc/articles/PMC2441794/ /pubmed/18450816 http://dx.doi.org/10.1093/nar/gkn231 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Molecular Biology
Simon, Philippe
Cannata, Fabio
Perrouault, Loïc
Halby, Ludovic
Concordet, Jean-Paul
Boutorine, Alexandre
Ryabinin, Vladimir
Sinyakov, Alexandre
Giovannangeli, Carine
Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates
title Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates
title_full Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates
title_fullStr Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates
title_full_unstemmed Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates
title_short Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates
title_sort sequence-specific dna cleavage mediated by bipyridine polyamide conjugates
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441794/
https://www.ncbi.nlm.nih.gov/pubmed/18450816
http://dx.doi.org/10.1093/nar/gkn231
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