Glycoscience and new drug design

Mechanistic and inhibition studies of essential enzymes involved in bacterial cell wall biosynthesis and colonization processes

Principal Investigator

Prof. Stéphane Vincent

UNamur, Department of chemistry, Unit of organic chemistry (UCO), Laboratory of bio-organic chemistry (CBO) 

Member of the Namur Research Pole in Infectiology (NaRePI)

Member of the Namur Institute of Structured Matter (NISM)

Research portal UNamur  |  ORCID  |  LinkedIn

Expertise and research interests

Prof. Stéphane Vincent leads a research group in bio-organic chemistry, with a special emphasis in glycoscience, biocatalysis and mechanistic enzymology. His team conducts mechanistic and inhibition studies of essential enzymes involved in the bacterial cell wall biosynthesis and the colonization processes by important human pathogens. The lab is specialized in the multi-step synthesis of complex glycoconjugates: nucleotide-sugars, glycofullerenes, glycolipids and functionalized carbohydrates. They develop their own inhibition assays.

Stéphane Vincent’s research activities focus on four main topics:

  1. Tuberculosis: Inhibition and mechanistic studies of the biosynthesis of galactofuranose, with the goal to develop new therapeutic strategies against tuberculosis
  2. Glycoclusters: Glycofullerenes as inhibitors of bacterial glycosyltransferases and as anti-adhesion molecules
  3. Antivirulence: Synthesis of inhibitors of the LPS (lypoPolySaccharide) biosynthetic pathway
  4. Biosensors for bacterial detection

Group members

Postdoctoral researchers: Dr. Timothé Vucko, Dr. Ignacio Bucheli, Dr. Maha Rzeigui, Dr. Kévin Renault

PhD students: Arnaud Beaufays, Jun Cao, Léa Chartier, Loïc Chêne, Andrei Diaconu, Jenny Ha and Marine Lacrictick

Research projects

  • ONGOING Synthesis of borylated glycomimetics. Ongoing PhD thesis by Jenny Ha. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • ONGOING Synthesis of fluorinated molecules for PET-Scan imaging. Postdoctoral research by Dr. Maha Rzeigui. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • ONGOING Development of rapid diagnostic tools for detection of antibiotic-resistant bacteria. Ongoing PhD thesis by Arnaud Beaufays. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • ONGOING Development of methodology to synthesized fluorinated sugar derivate. Postdoctoral research by Dr. Kévin Renault. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • ONGOING Synthesis of a novel Nickel pincer nucleotide and its biosynthetic precursors. Postdoctoral research by Dr. Timothé Vucko and previously Dr. Elsa Tufenkjian. Under co-supervision by Prof. Stéphane Vincent, UNamur (promoter) and Prof. Patrice Soumillon, UCLouvain (co-promoter).
  • ONGOING Synthetic inhibitors targeting polysaccharides biosynthesis as potential alternatives to antibiotherapy. Postdoctoral research by Dr. Ignacio Bucheli. Under co-supervision by Prof. Stéphane Vincent, UNamur (promoter) and Prof. Charles Gauthier and Prof. Eric Déziel, Université du Québec, Canada (co-promoters).
  • ONGOING Development of new technologies for antibodies functionalization. Ongoing PhD thesis by Léa Chartier. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • ONGOING Synthesis of Novel Heptose Derivatives as Antibacterial and Antivirulence Agents. Ongoing PhD thesis by Jun Cao. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • ONGOING Synthesis of new molecular probes to identify and label bacteria such as Brucella. Ongoing PhD thesis by Marine Lacritick. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS. In close collaboration with Prof. Xavier De Bolle, UNamur, NARILIS.
  • ONGOING Synthesis of sugar derivatives for the charaterization of Mycobacterium tuberculosis beta-D-Galactosyl-Hydrolases. Ongoing PhD thesis by Loïc Chêne. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • ONGOING Development of new materials with antibacterial, atibiofilm and drug delivery properties. Ongoing PhD thesis by Andrei Diaconu. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • Glycofullerenes as intra and extracellular enzymes inhibitors. Postdoctoral research by Ravikumar Jimmidi. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.
  • Synthesis of Novel Heterovalent Scaffolds as Antibiofilm Agents. Postdoctoral research by Dr. Tharwat Mohy El Dine. Under the supervision of Prof. Stéphane Vincent, UNamur, NARILIS.

Selected publications

Mohy El Dine T, Jimmidi R, Diaconu A, Fransolet M, Michiels C, De Winter J, Gillon E, Imberty A, Coenye T, Vincent SP. Pillar[5]arene-Based Polycationic Glyco[2]rotaxanes Designed as Pseudomonas aeruginosa Antibiofilm Agents. J Med Chem. 2021 Sep 20.

Diaconu A, Coenye T, Barboiu M, Vincent SP. Dynamic Constitutional Frameworks as antibacterial and antibiofilm agents. Angew Chem Int Ed Engl. 2021 Aug 4.

Fu J, Fu H, Xia Y, N'Go I, Cao J, Pan W, Vincent SP. Identification of inhibitors of UDP-galactopyranose mutase via combinatorial in situ screening. Org Biomol Chem. 2021 Feb 10.

Chen W, Mohy Ei Dine T, Vincent SP. Synthesis of functionalized copillar[4+1]arenes and rotaxane as heteromultivalent scaffolds. Chem Commun (Camb). 2020 Dec 16.

Liang L, Wade Wei TY, Wu PY, Herrebout W, Tsai MD, Vincent SP. Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling. Chembiochem. 2020 Oct 15;21(20):2982-2990.

Delbrouck JA, Bochatay VN, Tikad A, Vincent SP. Regioselective Synthesis of Difluorinated C-Furanosides Involving a Debenzylative Cycloetherification. Org Lett. 2019 Jul 19;21(14):5562-5566.

Frédéric CJ, Cornil J, Vandamme M, Dumitrescu L, Tikad A, Robiette R, Vincent SP. Highly ( Z)-Diastereoselective Synthesis of Trifluoromethylated exo-Glycals via Photoredox and Copper Catalysis. Org Lett. 2018 Nov 2;20(21):6769-6773.

Fu J, Fu H, Dieu M, Halloum I, Kremer L, Xia Y, Pan W, Vincent SP. Identification of inhibitors targeting Mycobacterium tuberculosis cell wall biosynthesis via dynamic combinatorial chemistry. Chem Commun (Camb). 2017 Sep 26;53(77):10632-10635.

Liang L, Vincent SP. Synthesis of D-glycero-D-manno-heptose 1,7-bisphosphate (HBP) featuring a β-stereoselective bis-phosphorylation. 2017 Tetrahedron Letters. 58, 37, p. 3631-3633.

Villaume SA, Fu J, N'Go I, Liang H, Lou H, Kremer L, Pan W, Vincent SP. Natural and Synthetic Flavonoids as Potent Mycobacterium tuberculosis UGM Inhibitors. Chemistry. 2017 Aug 1;23(43):10423-10429.

Frédéric CJ, Tikad A, Fu J, Pan W, Zheng RB, Koizumi A, Xue X, Lowary TL, Vincent SP. Synthesis of Unprecedented Sulfonylated Phosphono-exo-Glycals Designed as Inhibitors of the Three Mycobacterial Galactofuranose Processing Enzymes. Chemistry. 2016 Oct 24;22(44):15913-15920.

ALL PUBLICATIONS

Contact

stephane.vincent@unamur.be