Research

Thesis title: "Development of glycomimetic ligands for C-type lectin receptors"

Thesis outline: C-type lectin receptors (CLRs) are carbohydrate-binding proteins which are widely found in diverse organisms and have multiple functions, including immune response, cell-cell adhesion, and apoptosis. Thus, the development of CLRs targeting ligands is of promising prospect and will pave the way for CLRs corresponding therapeutic applications, like transcutaneous vaccine.
This project aims at the development of carbohydrate-based glycomimetic ligands for 5 representative immune regulation corresponding CLRs: porcine Langerin, human Langerin, murine Langerin, DC-SIGN, and Dectin-2. The design and synthesis of glycomimetics targeting ligands follow a heparin-inspired strategy reported by Rademacher group. N-acetylglucosamine derivatives are synthesized in 10 steps with commercially available glucosamine as starting material. Position 2 and position 6 are used to generate a library of N-acetylglucosamine derivatives with different functional groups (amide, amine, triazole, sulfonamide, etc.) and substitutions (aliphatic and aromatic). The necessary fluorine reporters for ¹⁹F NMR assay of each receptor are synthesized correspondingly. Since all designed acetylglucosamine derivatives are equipped with -CH₂-CH₂-NH₂ side chain at position 1 as a linker, advantageous ligands with higher affinity in biophysics assay are easily submitted to glycolipids synthesis and liposome formulation for cell-based assay.

Supervisor: Christoph Rademacher, Advisors: Natalija Simonović, Iris Bermejo

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