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Study of galectin-glycan interactions using fluoroglycomimetics

  • Duration:
    1/2023 - 12/2025
  • Provider:
    Grantová agentura České republiky
  • Programme:
    Standardní projekty
  • Registration number:
  • Principal Investigator:
  • Co-investigators:

    Spoluřešitel: Dr. rer. nat. Viktoria Heine (Mikrobiologický ústav AV ČR, v. v. i.)


Non-covalent recognition of glycans by galectins mediate or modulate numerous (patho)

biological processes including immune regulation, cancer, and fibrotic diseases. Using

monovalent and polyvalent fluorinated carbohydrates has emerged as an attractive way to

investigate glycan binding and develop selective inhibitors. In this grant proposal, we suggest

chemical and/or chemoenzymatic synthesis of series of fluorinated analogs of disaccharides

lactose, N-acetyllactosamine and N,N-diacetyllactosamine, and tetrasaccharide LacNAc1‑3Lac

and their use to investigate binding interactions with a panel of human galectins in both

monovalent and multivalent (after attachment to dendrimers and proteins) setting. Kinetic and

thermodynamic parameters of galectin binding will be determined and molecular basis of the

binding phenomena and oligosaccharide conformation investigated by NMR methods. On the

basis of recent findings by our team and others, we expect to modulate selectivity and affinity by

deoxyfluorination and ligand clustering, and identify selective and high affinity inhibitors.

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