Research

Mammalian glycan-binding proteins are involved in cell migration, pathogen recognition, uptake and processing, and determine many aspects of cellular communication. Strikingly, many of these receptors are uniquely expressed on defined immune cell subsets allowing to specifically address these cells in their complex biological environment. Hence, these cells, initiators and regulators of an effective immune response, are attractive targets immunotherapeutic approaches. Consequently, small molecule modulators of these carbohydrate-protein interactions would be beneficial for basic research and therapeutic intervention. Unfortunately, carbohydrate-binding sites are often rather featureless and flat and are therefore considered either challenging or undruggable, hampering the development of small molecule inhibitors. Additionally, only a limited number of high throughput screening attempts have been successful against this class of biomolecules.

Our work is concerned with the development of glycan receptor-specific ligands primarily resulting from fragment-based screening approaches using biophysical assays such as ¹⁹F NMR, STD NMR, ¹⁵N HSQC NMR, and SPR. These assays are complemented by in silico approaches as well as screening on chemical fragment microarrays and also by a recently developed cell-based assay that allowed screening our fragment library. Based on these chemical probes resulting from fragment-based design, we explore basic immunological questions as well as applied aspects such as small molecule targeted delivery of stimulants to specific immune cell subsets.

In particular, we have focused on: 

• Structure and Function of C-type Lectin Receptors
• Small Molecule-Mediated Targeted Delivery to Langerhans cells
• Glycan-Based Cell-Cell Communication
• Small Molecular Modulators of C-type Lectin Receptors
• Inhibitors of Bacterial Lectins
• Allostery in Drug Discovery