Chemical and chemoenzymatic syntheses of carbohydrates for therapeutic evalutions and immunological studies

现在很难遇到一个生活在加拿大的人没有因为癌症而失去亲人。在上个世纪，癌症曾经是一种罕见的疾病，但它已经迅速发展并成为仅次于心脏病的第二大常见死亡原因。在加拿大，癌症现在杀死了27%的男性和23%的女性，统计数据预测，今天的加拿大人口患癌症的风险要高得多;每2.4名男性中就有一名，而每2.7名女性中就有一名在一生中患癌症。碳水化合物是帮助我们了解癌症和传染病的起源、发展和增殖的关键，因为它们是在各种细胞间通讯和信号转导中发挥核心作用的主要介质分子。研究蛋白质-碳水化合物，碳水化合物-碳水化合物相互作用可以使我们能够设计和合成有效的治疗药物，可以靶向这些疾病所依赖的关键途径。我们研究的长期目标是开发和应用现代合成碳水化合物化学和生物有机化学来理解肿瘤发生，癌症转移和感染中涉及的碳水化合物-蛋白质相互作用，并设计，肿瘤相关哺乳动物和微生物碳水化合物抗原的合成和免疫学评价。在中短期内，我们计划开展以下方面的基础研究：1.合理设计和合成肿瘤相关糖基转移酶抑制剂; 2.制备高亲和力的寡唾液酸疫苗抗体，用于癌症治疗和感染性疾病预防; 3.提高糖类抗原免疫原性的有效聚类策略。

It is hard nowadays to meet someone living in Canada who has not lost someone close to them from cancer. During last century, once a rare disease, cancer has quickly evolved and become the second most common cause of mortality, next to heart disease. Cancer now kills 27% of men and 23% of women in Canada, and statistics has predicted a much higher risk to acquire cancer for today's Canadian population; one in every 2.4 males versus one in every 2.7 females will develop cancer in their lifetime. Carbohydrates hold the key in helping us understanding the origin, development and proliferation of cancer as well as infectious disease as they are primary mediator molecules playing central roles in all sorts of cell-cell communication and signal transduction. Studying protein-carbohydrate, carbohydrate-carbohydrate interactions can enable us to design and synthesize effective therapeutics that can target the crucial pathways these diseases rely on.OBJECTIVESThe long term objectives of our research are to develop and apply modern synthetic carbohydrate chemistry and bioorganic chemistry to the understanding of carbohydrate-protein interactions involved in tumorigenesis, cancer metastasis and infection, and to the design, synthesis and immunological evaluation of tumour-associated mammalian and microbial carbohydrate antigens. In the short to medium term, we plan to conduct basic research in the following areas:1.Rational design and synthesis of inhibitors for tumour-associated glycosyltransferases;2.Raising high affinity antibodies against oligosialic acid-based vaccines for the treatment of cancer and prevention of infectious disease3.Efficient clustering strategies for improving immunogenicity of carbohydrates antigens.