Human Intestinal Glucosidases: Counter-screening of novel therapeutics

Alectos Therapeutics是一家从位于卑诗省伯纳比的西蒙弗雷泽大学分拆出来的公司，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是针对调节参与合成或分解糖复合物（称为聚糖）的酶。这些可能被应用于日益增长的健康问题，包括阿尔茨海默氏症和帕金森氏症以及其他神经系统疾病。聚糖在我们的身体中无处不在，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，重要的是任何新的化合物都没有可能影响正常活动的副作用。该项目的目标是帮助公司筛选针对重要聚糖加工酶的新治疗 ** 化合物，以确保没有不必要的影响。这里研究的酶位于人类肠道中，是将我们饮食中的主要成分淀粉和蔗糖分解为葡萄糖提供能量的主要活动。这些酶，** 麦芽糖酶-葡糖淀粉酶（MGAM）和蔗糖酶-异麦芽糖酶（SI）的抑制将导致严重的后果，如 ** 严重的食物不耐受。该提案的目标是为Alectos提供大量的这些酶，用于交叉筛选它们有前途的化合物。由于这些酶是大的人类蛋白质，它们必须在真核细胞中产生，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制备酶。这笔资金将允许 ** 生产足够数量的两种人类肠道酶，以供公司进行交叉筛选。如果发现 ** 有害的活性，申请人将协助公司调查这些活性的原因 ** 并提高其化合物的特异性。

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.