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

合成生物活性低聚糖和糖复合物以引发碳水化合物特异性免疫反应并增强分子识别

• 批准号: 341532-2012
• 负责人: Ling, ChangChun
• 金额: $ 2.55万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632767
• 关键词: Synthesis; Bioactive; Oligosaccharides; Glycoconjugates; Elicit

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.

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。它们还产生许多种基于碳水化合物的聚合物，这些聚合物具有重要的功能，例如逃避宿主的免疫攻击，增强细胞活力和感染性。近年来，关于细菌对常用抗生素治疗的耐药性的报告以惊人的速度增加，包括金黄色葡萄球菌和空肠弯曲杆菌在内的许多细菌菌株;这两种病原体影响全球数亿人口。例如，仅在美国，现在就有更多的人死于医院获得性耐甲氧西林沙门氏菌感染。而不是艾滋病毒/艾滋病。因此，迫切需要开发有效对抗细菌感染的新型抗菌策略。接种疫苗是治疗细菌感染的有效方法。本基金申请拟研究合成与S. aereus和C.空肠，并随后评估用作疫苗以产生特异性抗体的潜力。此外，本申请还提出开发可行的合成方法以获得α-Kdo糖苷以及水溶性尼龙。重要的是研究α-Kdo糖苷的化学，因为它们是在所有革兰氏阴性细菌的脂多糖中发现的关键元素;与水溶性尼龙相关的项目具有产生新型多价支架的潜力，所述支架是水溶性的、可生物降解的并且能够呈递生物活性分子以增强的结合亲和力与其宿主相互作用。