Arbeitsgebiete
Our research is focused on the development of molecules modulating disease-relevant carbohydrate–protein interactions in infection, inflammatory diseases, and cancer. Many biological processes in this context are mediated by lectin receptors of innate immune cells, such as macrophages and dendritic cells, which assume important roles in the initiation of innate and adaptive immune responses.
C-type Lectin Receptors
Small molecule glycomimetic ligands that selectively bind C-type lectin receptors (CLRs) can serve as inhibitors of viral entry, immunomodulatory agents, or tools for targeted delivery. These ligands can be grafted to oligo- or multivalent supports to obtain functional nanomaterials for therapeutic applications. We constantly aim to improve our ability to design efficient and selective glycomimetics by trying to gain deeper insight into carbohydrate–protein interactions on a molecular level. For this, we study protein–ligand binding thermodynamics and kinetics of mono- and multivalent compounds by various biophysical techniques.
Sialic acid-binding Ig-like lectins
Sialic acid-binding Ig-like lectins (Siglecs) are immune receptors that recognize sialic acid-containing glycans. Typically, sialoglycans serve as a self-associated molecular pattern providing a “don’t eat me” signal to the immune system. In a cancer setting, the genetic dysregulation of glycosylation often results in the hypersialylation of tumor cells, which contributes to the suppression of immune functions. We aim to target the sialoglycan–Siglec axis with small molecule glycomimetics in an effort to reactivate dormant immune cells in the tumor microenvironment.
Human Chitinase-like proteins
Human chitinase-like proteins (CLPs) have evolved from chitin-degrading enzymes to assume pleiotropic functions related to immune homeostasis, cell proliferation, and tissue remodeling. Dysregulation of CLPs is linked to inflammation, fibrosis, and cancer. Their wide-ranging ability to modulate cellular processes is fully independent of chitin recognition and instead proceeds via the activation of cellular signal transduction cascades. However, ligands binding to the preserved chitin binding site can still modulate disease-relevant CLP functions. We are interested in elucidating the mechanism of chitin oligosaccharide and small molecule recognition in CLPs to explore their therapeutic potential.
Multivalent Glycoconjugates
Natural glycans presented on cell surfaces usually comprise repeated units of complex oligosaccharides. Thus, lectin receptors have evolved to recognize these multivalent displays, not monomeric carbohydrates, with high affinity. As a consequence, the presentation of monovalent glycomimetics on an oligo- or multivalent support can drastically improve the binding affinity of lectin ligands. A particular challenge in the design of those molecules is the choice of appropriate linker moieties. With the help of various biophysical techniques, we aim to improve our understanding of the correlation between structural features of linker moieties with the solution properties of the ligands and the energetics of receptor binding to provide the means for a more rational ligand design process.
GlycoDETECT: Detecting Carbohydrate Signatures of Circulating Tumor Cells
A key step in the development of metastasis is the ablation of tumor cells from the primary tumor and their dissemination through the bloodstream. Detection and isolation of circulating tumor cells (CTCs) from peripheral blood samples enables their use as potent prognostic markers for tracking treatment efficacy. We are developing chemical tools for this task based on the carbohydrate usage and glycan signatures of CTCs.
