P5: Sulfated natural polyglycosides and their non-glycosidic synthetic mimetics as multitarget ligands in (immuno)oncology

The Bendas group has extensively contributed to identify novel targets of heparin and synthetic mimetics in an oncological context with a focus on matricellular ligands, adhesion receptors, chemoresistance signaling, and platelet activation processes using cell biological and biosensor-based approaches

Although the polymeric structure and natural heterogeneity of sulfoglycosides complicates rational optimization and profiling, the sulfated polymer scaffold has turned out to be essential for biological effects. Recently, the Bendas group studied homo- and copolymers of sulfonated and carboxylated non-carbohydrate monomers, synthesized via reversible addition-fragmentation chain transfer polymerization, and investigated their effects on tumor-host cell interactions.

This led to the first report on highly potent heparin mimetics that interfere with platelet activation or cell adhesion and shed new light on such macromolecules as functional and tunable ligands. The aim of this project is the elucidation of structural characteristics and requirements of sulfated polymers as ligands for selected oncology targets to obtain novel bioactive molecules and tools for target validation.

Structurally modified heparins and synthetic sulfated polymers, varying in size, composition, and conformation, and fluorophore-tagged analogues will be investigated for their effects on tumor cell communication in a cellular (platelets, endothelium) and non-cellular microenvironment (matrix proteoglycans) by e.g. microscopic, biosensor or fluorescence (FRET) techniques.

Furthermore, their impact on tumor-shifted immune balance will be studied addressing the chemokine network, epigenetic targets (with P2), and ectonucleotidases (with P9). Moreover, effects on T-cell differentiation and activation will be elucidated in collaboration with P8.