2021-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/652864利用小分子來增加特定蛋白的穩定性是目前的一個新的藥物治療領域，有兩種方式可以用用於人類疾病的治療。首先是經由小分子結合在發生突變的蛋白，使得突變蛋白在內質體的折疊可以變好，蛋白能夠成熟然後被送到需要它工作的地方。再來是用小分子來穩定注入人體的蛋白質藥物。龐貝氏症(Pompe disease)是一種容小體儲積症，因為缺乏一種酵素叫做acid α-glucosidase (GAA)，使得全身組織中的溶小體都會發生肝醣的堆積。在這個計畫中，我們將去開發新的穩定GAA的小分子藥物，用natural product inspired combinatorial chemistry的方法來進行。我們將用龐貝氏症的小鼠及大鼠來測試所研發出的分子的效能，以及最佳的治療方式。我們希望研發出來的藥物能對龐貝氏症的治療有所幫助。 The stabilization of specific proteins using small molecules is an emerging strategy in drug development, and this strategy has two main applications in human diseases. First, small molecules specifically bind to mutant enzyme proteins in ER and assist their correct folding, maturation, and trafficking to their destination site. Second, small molecules to suppress the intrinsic instability of exogenous protein drugs. Pompe disease is a lysosomal storage disorder with deficiency of acid α-glucosidase (GAA) which causes the lysosomal accumulation of glycogen in all tissues. In this project, we will develop new GAA protein stabilizers through our natural product inspired combinatorial chemistry approach. We will use Pompe mice and rat to test the efficacy of novel GAA stabilizers and then identify the best compound and treatment method for Pompe disease. We expected to create new molecules which can help the treatment of Pompe disease.龐貝氏症酵素補充治療侶伴蛋白Pompe diseaseacid alpha-glucosidaseenzyme replacement therapychaperone