Development of carbohydrate analogues as mechanistic probe for the characterization of galactofuranoside hydrolase

Candidate

Loïc CHENE

Promoter

Prof. Stéphane VINCENT, UNamur, Department of chemistry, Laboratory of bio-organic chemistry (CBO)

Jury

• Prof. Steve LANNERS (département de chimie, UNamur), président
• Prof. Stéphane VINCENT (département de chimie, UNamur), promoteur et secrétaire
• Prof. Bruno LINCLAU (Department of Organic and Macromolecular Chemistry, UGent)
• Prof. Olivier RIANT (département de chimie, UCLouvain)
• Prof. Johan WOUTERS (département de chimie, UNamur)

Summary

Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (Mtb), is an infectious disease that generally affects the lungs. Since the past decades, World Health Organization declared TB a global public health emergency.

The main hurdle of the total eradication of TB is the over- or misuse and antibiotic drugs, which favour the development of drug resistant strains of TB. This resistance to effective treatment increases the urge to find new therapeutic agents to cure tuberculosis, as well as new biological targets.

The most targeted feature of TB is its cell wall. A wide range of enzymes, responsible of the cell wall biosynthesis, have already proven efficiency in decreasing the mycobacterial virulence and survival.

Recently, researchers found a novel enzyme involved in the degradation of the cell wall. It was described as an exo-b-D-galactofuranosidase (GlfH1), responsible of the catabolism of the arabinogalactan (AG) part of the membrane.

During this PhD, we focused on the synthesis of novel mechanistic probes, to characterize this new biological target. To do so, synthesises based on mono- and polyfluorinated carbohydrate and carbasugar strategies have been developed and tested against GlfH1.