Mechanism-Based Carbohydrate Chemistry and Biochemistry

基于机制的碳水化合物化学和生物化学

• 批准号: 121348-2012
• 负责人: Bennet, Andrew
• 金额: $ 5.1万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569177
• 关键词: Mechanism; Based; Carbohydrate; Chemistry; Biochemistry

The research outlined in this proposal involves two main areas of carbohydrate (sugar) chemistry. We plan to investigate the fundamental aspects of the biological reactions of carbohydrates and how they deviate from the corresponding reactions in water. Organisms are complex entities whose very existence depends on the ability to metabolize (breakdown) various dietary nutrients. Two distinct phases of metabolism exist: (1) energy-yielding catabolic processes that involve the degradation of complex food sources such as carbohydrates, proteins, and fats to produce simpler molecules; and (2) anabolism, that phase that is concerned with natural processes in which simple components, such as glucose are used to form more complex molecules that are required for the growth and survival of an organism. These two types of metabolic pathways employ enzymes that are either specific for degradation-type reactions, or that function in reactions which lead to the assembly of complex molecules. A goal of this project is to design inhibitors for both types of sugar processing enzymes because many of these enzymes are implicated in various ailments including tuberculosis and Fabry's disease. The inhibitors made during the course of this program of research will have the potential to become therapeutic agents. A second goal of this proposal is to apply the fundamental information gained from the carbohydrate reaction studies to the modification of sugar-catabolizing enzyme (a glycosidase) so that it can target different sugars. What would be the advantage of modifying a glycosidase in this way? Information gleaned from this study will allow researchers to get a better understanding of biological evolution and how nature slowly, but inexorably, improves enzyme efficiency.

该提案中概述的研究涉及碳水化合物（糖）化学的两个主要领域。 我们计划研究碳水化合物生物反应的基本方面，以及它们如何偏离水中的相应反应。 生物是复杂的实体，其存在的存在取决于代谢（分解）各种饮食营养素的能力。 存在两个不同的代谢阶段：（1）能量赋予分解代谢过程，涉及复杂食品源的降解，例如碳水化合物，蛋白质和脂肪，以产生更简单的分子； （2）合成代谢，与自然过程有关的阶段，其中简单成分（例如葡萄糖）用于形成有机体生长和生存所需的更复杂的分子。 这两种类型的代谢途径采用特定于降解型反应的酶，或者在导致复杂分子组装的反应中的功能。 该项目的一个目的是为这两种类型的糖加工酶设计抑制剂，因为这些酶中的许多都与各种疾病有关，包括结核病和Fabry病。 在此研究计划期间所产生的抑制剂将有可能成为治疗剂。 该提案的第二个目标是将从碳水化合物反应研究中获得的基本信息应用于糖促糖酶（一种糖苷酶）的修饰，以便它可以靶向不同的糖。 以这种方式修饰糖苷酶的优势是什么？ 从这项研究中收集的信息将使研究人员能够更好地了解生物学进化以及自然如何缓慢，但无情地提高了酶效率。