Human Intestinal Glucosidases: Counter-screening of novel therapeutics

Alectos Treateutics是从不列颠哥伦比亚省本纳比的西蒙·弗雷泽大学剥离出来的一家公司，致力于**开发治疗严重疾病的新疗法。这些化合物中的大多数都是用来调节参与糖类复合体的合成或分解的酶，这些复合体称为多糖。这些可能会被**用于日益严重的健康问题，包括阿尔茨海默氏症、帕金森氏症和其他神经疾病。**多糖在我们体内无处不在，而制造或降解它们的酶对**健康的许多方面都是必不可少的。因此，重要的是，任何新化合物都不能有可能**影响正常活动的副作用。该项目的目标是帮助该公司筛选针对重要的糖链加工酶的新的治疗性化合物，以确保没有不必要的影响。**这里研究的酶位于人体肠道，是将淀粉和蔗糖--我们饮食的主要成分--分解为葡萄糖以获取能量的主要活动。抑制这些酶，**麦芽糖酶-糖淀粉酶(MGAM)和蔗糖酶-异麦芽糖酶(SI)，将导致严重的后果，如**严重的食物不耐受。该提案的目标是为Alectos提供大量这些酶，以**交叉筛选它们有希望的化合物。由于这些酶是大的人类蛋白质，它们必须**在真核细胞中生产，以确保天然活性。**申请人的实验室正在酵母细胞培养系统中准备这些酶。这笔资金将允许**生产足够数量的两种人体肠道酶，供该公司进行交叉筛选。如果看到**有害的活动，申请人将协助公司调查这些活动的原因**并改进其化合物的专属性。

Alectos Therapeutics, a spin-off company from Simon Fraser University in Burnaby, BC, is dedicated to the**development of novel therapeutics for serious diseases. Most of these compounds are targeted to regulate**enzymes involved in the synthesis or breakdown of sugar complexes called glycans. These could potentially be**applied to growing health concerns, including Alzheimer's and Parkinson's Diseases and other neurological**conditions.**Glycans are present everywhere in our body, and the enzymes that make or degrade them are essential to**many aspects of health. Therefore, it is important that any new compounds do not have side-effects that could**affect normal activities. The goal of this project is to assist the company in screening their new therapeutic**compounds against important glycan processing enzymes, to make sure there are not unwanted affects.**The enzymes under study here are located in the human intestine and are the primary activities for breaking**down starch and sucrose, major components of our diet, into glucose for energy. Inhibition of these enzymes,**maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), would lead to serious consequences, such as**major food intolerances. The goal of the proposal is to provide Alectos with quantities of these enzymes for**cross-screening their promising compounds. As these enzymes are large, human proteins, they have to be**produced in eukaryotic cells, to ensure native activity.**The applicant's laboratory is preparing the enzymes in a yeast cell culture system. The funding would allow**production of sufficient quantities of both human intestinal enzymes for cross-screening by the company. If**unwanted activities are seen, the applicant will assist the company in investigating the causes of those activities**and improving the specificity of their compounds.