Soutenance publique de thèse de doctorat en Sciences chimiques - Marine Lacritick

Clickable mannose analogues: powerful tool to label bacterial cell wall by Metabolic Glycoengineering and Synthesize sugar nucleotide for antibodies functionalization

Jury

• Prof. DE BOLLE Xavier (UNamur), President
• Prof. VINCENT Stéphane (UNamur), Secretary
• Prof. BOLTJE Thomas (Radboud University)
  
• Prof. GUIANVARC’H Dominique (Paris-Saclay University)
• Prof. WOUTERS Johan (UNamur)

Abstract

 

Mannose is a carbohydrate that we can naturally find in some bacterial cell envelope, more precisely in lipopolysaccharide core. To explore the metabolic route of this natural sugar: Metabolic Gylcoengineering (MGE) has been employed for studying biomolecules in living systems. We aim to chemically modify the cell surfaces to install unnatural monosaccharides that are metabolically transformed and incorporated by microorganisms. The metabolic incorporation into glycans pathway can be visualized by biorthogonal click reactions with fluorescent reporters that can bind to unnatural carbohydrates. In this project, the strategy is to synthesize several mannose derivatives to target the metabolic route of D-mannose and explore the glycosylation pathway in Gram-negative bacteria.

On top of that, another application is to apply this clickable mannose as an interesting building block to synthesize nucleotide sugar for antibodies (Ab) functionalization. Indeed, antibody-drug conjugates (ADC) constitute a new emerging class of highly potent pharmaceutical drugs, especially in cancer therapy. The aim is to perform regioselective modification in antibody’s subunit containing glycan chains from GDP-mannose derivative. This latter must be synthesized and tested as unnatural mannose donors for glycosyltransferase that catalyzes the transfer of sugar moiety to mannose acceptor in specific site of the antibody

 

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