" Soutenance de thèse de Jihen ATI. | Université d'Orléans

Université d'Orléans

Soutenance de thèse de Jihen ATI.

11/12/2018 - 09:30 - 11/12/2018 - 13:00

URL: http://www.univ-orleans.fr/actus/soutenances

Nom du contact: Etudes Doctorales

Courriel du contact: etudes.doctorales@univ-orleans.fr

Lieu: Salle des thèses - UFR Collegium Droit, Economie, Gestion - rue de Blois - campus UNIVERSITÉ

Titre :  Leishmanian Galactofuranosyltransferases as promising versatile tools for therapeutic and chemoenzymatic approaches.

Discipline : Biochimie

ECOLE DOCTORALE SSBCV

Résumé :

Cells are heavily decorated by diverse glycoconjugates that are involved in important biological events such as cell-cell communication, growth of healthy or cancerous cells and pathogens infection process. Among these polysaccharidic structures, Galf-containing glycans have been the subject of increasing interest in the last decades. Indeed, the galactofuranose can be found in many pathogenic species, such as Mycobacterium tuberculosis, Aspergillus and Leishmania, but is absent in mammals. Therefore, these glycoconjugates are considered as interesting targets for therapeutic approaches.Galactofuranosyltransferases (GalfTs) catalyse the transfer of galactofuranose residues into glycoconjugates structures. However, GalfTs are poorly described enzymes despite their crucial role in the virulence and the pathogenicity of numerous microorganisms. Up to date, only one mycobacterial GalfT has been fully characterized. In this thesis, four putative GalfTs of Leishmania major, the causing agent of leishmaniosis diseases, were characterized. They were first cloned, overexpressed in E. coli and purified. Then, their respective kinetic parameters were determined. In addition, since these GalfT are located in the Golgi apparatus of Leishmania, we assumed that their glycosylation could be an important element for their stability and activity. So, glycosylated GalfTs were produced using, Leishmania tarentolae, and preliminary results of their enzymatic activity were obtained. Still, leishmanian GalfTs demonstrate promising results for the development of new chemoenzymatic strategies for Galf-containing glycoconjugates synthesis, as well as the design of new drugs against leishmaniasis.