title: (19)F NMR-Guided Design of Glycomimetic Langerin Ligands.
abstract: C-type lectin receptors (CLRs) play a pivotal role in pathogen defense and immune homeostasis. Langerin, a CLR predominantly expressed on Langerhans cells, represents a potential target receptor for the development of anti-infectives or immunomodulatory therapies. As mammalian carbohydrate binding sites typically display high solvent exposure and hydrophilicity, the recognition of natural monosaccharide ligands is characterized by low affinities. Consequently, glycomimetic ligand design poses challenges that extend to the development of suitable assays. Here, we report the first application of (19)F R2-filtered NMR to address these challenges for a CLR, i.e., Langerin. The homogeneous, monovalent assay was essential to evaluating the in silico design of 2-deoxy-2-carboxamido-α-mannoside analogs and enabled the implementation of a fragment screening against the carbohydrate binding site. With the identification of both potent monosaccharide analogs and fragment hits, this study represents an important advancement toward the design of glycomimetic Langerin ligands and highlights the importance of assay development for other CLRs.
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Department of Biomolecular Systems, 14424 Potsdam, Germany.|Freie Universität Berlin , Department of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
authors.forename: Eike-Christian
authors.initials: EC
authors.lastname: Wamhoff
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Department of Biomolecular Systems, 14424 Potsdam, Germany.|Freie Universität Berlin , Department of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hanske
authors.affiliation: Freie Universität Berlin , Department of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
authors.forename: Lennart
authors.initials: L
authors.lastname: Schnirch
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Department of Biomolecular Systems, 14424 Potsdam, Germany.|Freie Universität Berlin , Department of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Aretz
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Department of Biomolecular Systems, 14424 Potsdam, Germany.|Freie Universität Berlin , Department of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
authors.forename: Maurice
authors.initials: M
authors.lastname: Grube
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Department of Biomolecular Systems, 14424 Potsdam, Germany.|Freie Universität Berlin , Department of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Varón Silva
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Department of Biomolecular Systems, 14424 Potsdam, Germany.|Freie Universität Berlin , Department of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Rademacher
mesh_terms: D015703:Antigens, CD / Q000737:chemistry*; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D037181:Lectins, C-Type / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D037241:Mannose-Binding Lectins / Q000737:chemistry*; D018716:Molecular Mimicry
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D002241:Carbohydrates; D037181:Lectins, C-Type; D008024:Ligands; D037241:Mannose-Binding Lectins; D005461:Fluorine