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Synthèse d’inhibiteurs d’endosulfatases humaines : vers de nouveaux outils thérapeutiques contre le cancer et les maladies inflammatoires

Abstract : Endosulfatases 1 and 2 belong to the sulfatase family and are enzymes that catalyse the 6-O-desulfation of Heparan Sulfate (HS), a polysaccharide highly sulfated belonging to the glycosaminoglycan family. HS chains interact with numerous signalling proteins including chimiokines, cytokines, growth factors ... through their sulfation pattern. By desulfating the HS chains, the endosulfatases play a key role in the signalling regulation and in the organism’s biological process. The human endosulfatase 2 (HSulf2) is over expressed in many cancers (breast, ovarian, pancreas, lungs ...) and represents thus an interesting therapeutic target. To obtain specific HSulf2 inhibitors, four oligosaccharides with different lengths, mimicking the HS chains with a sulfamoyl function were synthesised. To do so, a key step was optimised, the N, O-sulfonation. Then, the four molecules were tested to assess their capacity to inhibit HSulf2.To broaden the choice of potential HSulf2 inhibitors, monosaccharides with hydroxylamine and hydrazine function were synthesised.
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Submitted on : Tuesday, November 3, 2020 - 2:57:09 PM
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  • HAL Id : tel-02987041, version 1

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Pauline Quellier. Synthèse d’inhibiteurs d’endosulfatases humaines : vers de nouveaux outils thérapeutiques contre le cancer et les maladies inflammatoires. Chimie organique. Université Paris-Saclay, 2020. Français. ⟨NNT : 2020UPASF008⟩. ⟨tel-02987041⟩

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