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Etude du transporteur de multiples drogues MRP1 : caractérisation des NBD, et étude de modulateurs conduisant à la mort des cellules surexprimant le transporteur

Abstract : The acquisition of cancer resistance phenotype is mostly correlated to the expression of membrane transporters belonging to the ABC transporters super family (“ATP-Binding Cassette”). One of these transporters, MRP1 (“Multidrug Resistance Protein1”), is a transmembrane protein which has the ability to efflux many substrates.
First, this work has focused on the characterisation of the isolated nucleotide binding domains. A biochemical study has shown their asymmetric behaviour towards nucleotides, and their ability to bind substrates, which could lead to the involvement of NBDs in the substrate binding site.
Then, a characterisation of the verapamil enantiomers has been performed, showing that S-verapamil was responsible of glutathione efflux, whereas R-verapamil had an inhibitory effect on MRP1. These results may have great impact in term of therapy.
Finally, structure/function relationships of verapamil and flavonoids derivatives has been accessed, in order to find more potent modulators for MRP1.
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https://tel.archives-ouvertes.fr/tel-00340658
Contributor : Thomas Perrotton <>
Submitted on : Friday, November 21, 2008 - 3:31:17 PM
Last modification on : Thursday, November 21, 2019 - 2:02:15 AM
Long-term archiving on: : Monday, June 7, 2010 - 9:50:42 PM

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  • HAL Id : tel-00340658, version 1

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Thomas Perrotton. Etude du transporteur de multiples drogues MRP1 : caractérisation des NBD, et étude de modulateurs conduisant à la mort des cellules surexprimant le transporteur. Biochimie [q-bio.BM]. Université Claude Bernard - Lyon I, 2007. Français. ⟨tel-00340658⟩

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