Date of Degree
Adam B. Braunschweig
David R. Mootoo
Biochemistry | Organic Chemistry | Virology
carbohydrate, glycobiology, host-guest interactions, supramolecular chemistry
Carbohydrate – receptor interactions are often involved in the attachment of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered “undruggable”, meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs) – small molecules that bind carbohydrates – could bring carbohydrate-receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate-receptor interactions in viral infection, the evolution of SCRs, and recent results demonstrating their ability to prevent viral infections in vitro. Common SCR design strategies based on boronic-ester formation, metal chelation, and noncovalent interactions are discussed. The benefits of incorporating the idiosyncrasies of natural glycan binding proteins – including flexibility, cooperativity, and multivalency – into SCR design to achieve non-glucosidic specificity are shown. These studies into SCR design and binding could lead to new strategies to mitigate the grave threat to human health posed by enveloped viruses, which are heavily glycosylated viroids that are the cause of some of the most pressing and untreatable diseases, including HIV, Dengue, Zika, influenza, and SARS-CoV-2.
Bravo Carranco, Marcelo F., "Small Molecule Synthetic Carbohydrate Receptors" (2020). CUNY Academic Works.