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

碳水化合物在所有细胞间的通讯中起着至关重要的作用。细菌利用碳水化合物作为其生存、生长和繁殖的能量来源。它们还产生许多基于碳水化合物的聚合物，这些聚合物具有重要的功能，如逃避宿主的免疫攻击，提高它们的细胞活力和感染力。近年来，关于细菌对常见抗生素治疗的耐药性的报道以惊人的速度增加，许多细菌菌株，包括金黄色葡萄球菌和空肠弯曲菌；这两种病原体影响着全球数亿人口。例如，仅在美国，现在死于医院获得的耐甲氧西林金黄色葡萄球菌感染的人就比死于艾滋病毒/艾滋病的人多。因此，迫切需要开发新的抗菌策略来有效地对抗细菌感染。接种疫苗是治疗细菌感染的一种行之有效的方法。这项赠款申请计划研究与弧菌和空肠弯曲菌产生的特殊多糖相关的类似物的合成，并随后评估作为疫苗用于提高特定抗体的潜力。此外，申请还建议开发可行的合成方法来获得α-Kdo糖苷以及水溶性尼龙。研究α-Kdo糖苷的化学很重要，因为它们是所有革兰氏阴性细菌脂多糖中的关键元素；与水溶性尼龙相关的项目有可能产生新型的多价支架，这些支架是水溶性的，可生物降解的，并能够呈现生物活性分子，以增强结合亲和力与宿主相互作用。

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.