Synthesis of Bioactive Oligosaccharides and Glycoconjugates to Elicit Carbohydrate-Specific Immune Responses and Enhance Molecular Recognitions

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Carbohydrates play crucial roles in all cell-cell communications. Bacteria use carbohydrates as an energy source for their survival, growth and reproduction. They also produce many kinds of carbohydrate-based polymers that carry important functions such as evade an immunological attack from the host, enhance their cell viability and infectivity. During recent years, reports on bacterial resistance to common antibiotics treatment have increased at an alarming pace for many bacterial strains, including Staphylococcus aureus and Campylobacter jejuni; both pathogens affect hundreds of millions of populations worldwide. For example, in the US alone, more people now die from infections by hospital-acquired methicillin-resistant S. aureus than from HIV/AIDs. Therefore, there is an urgent need to develop novel antibacterial strategies that are effective to combat bacterial infections. Vaccination is a proven method to treat bacterial infections. This grant application proposes to study the synthesis of analogs related to special polysaccharides produced by S. aereus and C. jejuni, and subsequently evaluate the potential to be used as vaccines for raising specific antibodies. Additionally, the application also proposes to develop viable synthetic methodologies to obtain alpha-Kdo glycosides as well as water-soluble nylons. It is important to study the chemistry of alpha-Kdo glycosides as they are key elements found in lipopolysaccharides of all Gram-negative bacteria; the project related to water-soluble nylons has the potential to generate novel multivalent scaffolds that are water-soluble, biodegradable and capable of presenting bioactive molecules to interact with their host with enhanced binding affinity.