Using Supramolecular Biomaterials to Interrogate and Manipulate Galectin-Glycan Interactions


Hudalla, Greg (University of Florida)


Covalent carbohydrate conjugates, referred to as glycans, decorate the surfaces of all mammalian cells and are found on nearly half of all mammalian proteins. Proteins that recognize specific glycan structures, known as lectins, play a central role in decoding the information stored within glycans and converting this information into signals that direct changes in cell behavior. Galectins are a specific subset of secreted lectins that can act as signaling molecules in healthy and pathological processes throughout all stages of life. Our research program employs supramolecular biomaterials as scaffolds to interrogate and manipulate galectin-glycan interactions. Supramolecular biomaterials are an ideal scaffold for these efforts because they allow us to mimic the multivalent architectures of galectins and glycans that are critical for their binding and biological activity. For example, we are developing beta-sheet peptide nanofibers modified with glycan appendages as synthetic glycoprotein mimetics. By tailoring glycan density or glycan chemistry on the nanofibers, we can tune their galectin binding affinity or specificity. We can use these glycopeptide nanofibers to disrupt or augment galectin signaling by changing the manner in which they are presented to cells (e.g. solution versus solid-phase). We also employ alpha-helical coiled-coils as scaffolds for multivalent galectin display. Using these scaffolds, we can create tools to study valency-function relationships of galectin-3. We can also use these scaffolds to create delivery vehicles that anchor a therapeutic enzyme at an injection site by endowing the enzyme with extracellular glycan-binding affinity. Finally, we can use coiled-coil scaffolds to create new anti-inflammatory therapeutics by recombining different galectins into non-natural multivalent architectures. Collectively, the examples presented in this talk will highlight the broad potential of supramolecular biomaterials to interrogate and manipulate galectin-glycan interactions, and identify new opportunities to exploit galectin-glycan interactions for tissue engineering.


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