Catalysis, Reactivity and Probe Development in Carbohydrate-Based Chemistry and Biochemistry

碳水化合物化学和生物化学中的催化、反应性和探针开发

• 批准号: RGPIN-2017-04910
• 负责人: Bennet, Andrew
• 金额: $ 6.56万
• 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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711291
• 关键词: Catalysis; Reactivity; Probe; Development; Carbohydrate

In living systems, such as ourselves, the addition and removal of sugars, which are also known as carbohydrates, is tightly regulated. That is, we use a lot of the energy that we get by eating carbohydrates to ensure that molecules within our bodies have the correct sugars attached to them. If this systems gets "out of whack" then serious diseases can ensue. This NSERC Discovery Grant proposal seeks funds for our research program that is concentrated on three areas of current interest in carbohydrate chemistry and biology. Firstly, we will investigate how a series of crucial enzymes (Nature's catalysts for performing reactions) add sugars to molecules by joining them together with a chemical bond. These enzymes are called sugar transferases and are important because some of them are implicated in many disease states including cancer. We wish to understand how these enzyme work in order that we can design molecules to prevent the transfer of sugars in specific cases, such as in cancer. Secondly, we will continue our efforts in making reactive non-sugar molecules, which we have designed to imitate carbohydrates. To date, our molecules have shown a dramatic ability to decrease (or inhibit) the activity of enzymes that remove sugars from carbohydrate chains such as those found in starch. Our new inhibitors will be tested in situations were enzyme activity is greater than it should be in normal individuals. That is, if we can lower the enzyme activity, by administering our molecules, to that of a non-diseased individual (normal level) then these compounds are potential therapeutic agents. Lastly, we will use the latest techniques in modern molecular biology to develop new enzyme catalysts. In this endeavour we are using our experience with an enzyme (called a sialidase) that regulates several critical processes of self-recognition, which is important since we don't want our immune system to attack us. We have over ten years of experience with sialidase enzymes and will use this experience to modify the enzyme so that it can be used to test for abnormalities in the carbohydrates that are attached to various cells. Such modified enzymes will be very useful tools for researchers who are interested in cell to cell communication, for example, a cell has to know whether its neighbor is also a Human cell. Our modified enzymes can also be used to test for various types of cancer as many cancer cells show an abnormal array of carbohydrates on their surfaces.

在生命系统中，比如我们自己，糖（也被称为碳水化合物）的添加和去除是受到严格控制的。也就是说，我们通过摄入碳水化合物获得大量能量，以确保我们体内的分子有正确的糖附着在它们上面。如果这个系统“不正常”，那么严重的疾病就会随之而来。这项NSERC发现拨款提案为我们的研究项目寻求资金，该项目集中在目前对碳水化合物化学和生物学的三个领域。