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Séminaire Chimie ED459

An epigenetic tool : 3-hydroxychromone (3-HC) as a fluorescent dye to study DNA methylation

Dr. Benoît Michel (Institut de Chimie de Nice, UMR 7272 CNRS, Université de Nice)

publié le

Le Jeudi 09 juillet 2015 à 13h45
UM FdS salle de cours SC-16.01 (campus Triolet)

DNA methylation is one of the major epigenetic modification and plays an important role in the regulation of major processes such as the maintenance of genome integrity, genomic imprinting, tissue-specific expression of genes, X chromosome inactivation and the « silencing » of transposons and retroviruses. On the other hand, alterations of the DNA methylation pattern are involved in the development of different diseases such as cancers, neurodegenerative disorders and genetic and metabolic diseases [1]. DNA methylation was recently recognized as one of the major target to inhibit and to fight cancer. Although several inhibitors have already been identified, their lack of selectivity, poor activity and toxicity limit their development. A deeper insight of the DNA methylation mechanism should help medicinal chemists in the design and research of more specific inhibitors of DNA methylation.

[see figure in attached PDF abstract]

Currently, miscellaneous hypothesis are advanced about the DNA methylation mechanism and deserve to be confirmed or clarified. In this context, we propose to develop new chemical tools, ratiometric fluorescent dyes, to study the dynamics and mechanism of DNA methylation. Among environmental sensitive probes, the 3-hydroxychromone (3-HC) family is a class of fluorophores that appears particularly promising. Indeed, 3-HCs are multiparametric and ratiometric fluorescent dyes that present two well-resolved bands in the emission spectrum and are highly sensitive to the environmental changes. Two different strategies of labeling DNA were explored. In the first one, the natural nucleobase was substituted by our fluorescent dye in order to probe inside the duplex. In this case, the biosensor was revealed to be a highly sensitive environment tool for probing at the molecular level, changes of polarity and H-bond donor ability of the surrounding environments. The second approach is based on a modification of a natural nucleobase on which, through a linker, the ratiometric probe was incorporated. By this way, the fluorescent reporter will sense the interactions in the major groove. Both approaches we have developed will be presented herein [2-5].

References

1. Martinet, N. et al. Med. Chem. Commun., 2012, 3, 263–273.
2. Spadafora, M. et al. Tetrahedron, 2009, 65, 7809–7816.
3. Dziuba, D. et al. J. Am. Chem. Soc. 2012, 134, 10209–10213.
4. Dziuba, D. et al. Chem. Eur. J. 2014, 20, 1998–2009.
5. N. P. F. Barthes et al. RSC Advances, 2015, 5, 33536–33545.

Contact local IBMM : Sébastien Ulrich

Agenda

séminaire

  • Jeudi 9 juillet 2015 de 13h45 à 15h00 -

    An epigenetic tool : 3-hydroxychromone (3-HC) as a fluorescent dye to study DNA methylation

    Résumé : Séminaire Chimie ED459 – Benoît Michel

    Lieu : UM FdS, salle SC-16.01


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