Human Intestinal Glucosidases: Counter-screening of novel therapeutics

Alectos Therapeutics是一家从不列颠哥伦比亚省本拿比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用来调节参与糖复合物（称为聚糖）合成或分解的酶的。这些技术有可能应用于日益严重的健康问题，包括阿尔茨海默病、帕金森病和其他神经系统疾病。聚糖存在于我们身体的任何地方，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影响正常活动的副作用。该项目的目标是协助该公司筛选针对重要聚糖加工酶的新治疗性化合物，以确保没有不必要的影响。这里研究的酶位于人体肠道内，是将淀粉和蔗糖（我们饮食的主要成分）分解成葡萄糖作为能量的主要活动。抑制麦芽糖酶-葡萄糖淀酵酶（MGAM）和蔗糖-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提供这些酶的数量，以交叉筛选其有希望的化合物。由于这些酶是大型的人类蛋白质，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。这笔资金将允许该公司生产足够数量的这两种人类肠道酶进行交叉筛选。如果发现**不需要的活性，申请人将协助公司调查这些活性的原因**并改善其化合物的特异性。

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.