alpha-葡萄糖苷酶与糖尿病、癌症和病毒感染等疾病有密切关系，该酶抑制剂的研制有可能发现新的药物；并且可能以此小分子抑制剂为探针，研究该酶的结构与功能。这是从糖化学及糖生物学的新视角出发，探索上述疾病的发病机制及药物治疗，是当前糖研究热点。.本项目将能被alpha-葡萄糖苷酶所识别的二糖底物-曲二糖作为被模拟对象，依据现有机理信息，设计用氮杂糖或氨基环多醇替换曲二糖还原端或非还原端葡萄糖基以模拟酶催化反应过渡态、进一步在氮原子上取代直链烷基和氨基酸残基以及通过碳苷键连接曲二糖两部分糖基以增加分子稳定性等结构修饰手段，合成一系列曲二糖类似物供活性筛选，以期发现高活性高选择性的先导化合物。该工作是在二糖基础上探索抑制剂的构效关系及酶催化机理，有望获取更加有用的信息，对深入研制alpha-葡萄糖苷酶抑制剂和解明该酶的结构与功能具有重要意义。

Alpha-glucosidase is closely associated with diabete, cancer and viral infection. Studies on the inhibitors of alpha-glucosidase lead probably to the discovery of new drugs, and these small molecular could be utilized as probes to investigate the structures and functions of alpha-glucosidase. This area, exploring the onset mechanism and drug therapy of the above diseases from the new insight of glycochemistry and glycobiology, has become the hot spot of the current carbohydrate research..In this project, we will employ the disaccharide substrate, i.e, kijibiose which can be recognized by alpha-glucosidase as mimic target to design and synthesize a series of derivatives according to the glucosidase-mediated hydrolysis mechanism for pharmacoscreening. Our ultimate aim is to find novel lead compounds possessing efficient inhibition of alpha-glucosidase with high selectivity. This strategy, based on the disaccharidic structure, is believed to acquire more useful information on the structure-activity relationship of the inhibitors and enzyme-catalyzed reaction mechanism compared with the current approaches.

alpha-葡萄糖苷酶与糖尿病、癌症和病毒感染等疾病有密切关系，该酶抑制剂的研制有可能发现新的药物；并且可能以此小分子抑制剂为探针，研究该酶的结构与功能。这是从糖化学及糖生物学的新视角出发，探索上述疾病的发病机制及药物治疗，是当前糖研究热点。本项目将能被alpha-葡萄糖苷酶所识别的二糖底物-曲二糖作为被模拟对象，依据现有机理信息，设计用氮杂糖或氨基环多醇替换曲二糖还原端或非还原端葡萄糖基以模拟酶催化反应过渡态、进一步在氮原子上取代直链烷基和氨基酸残基以及通过碳苷键连接曲二糖两部分糖基以增加分子稳定性等结构修饰手段，合成一系列曲二糖类似物供活性筛选，以期发现高活性高选择性的先导化合物。该工作是在二糖基础上探索抑制剂的构效关系及酶催化机理，有望获取更加有用的信息，对深入研制alpha-葡萄糖苷酶抑制剂和解明该酶的结构与功能具有重要意义。