Bifunctional Hybrid Enzyme-Catalytic Metal Organic Framework Reactors for α-Glucosidase Inhibitor Screening

The screening strategy based on α-glucosidase inhibition has been widely employed for the discovery of antidiabetic drugs, but it still faces some challenges in practical applications, such as poor stability of enzyme, high consumption of test compounds, low sensitivity of screening methods and so on. In this work, a bifunctional hybrid enzyme-catalytic metal organic framework reactor (GAA@GOx@Cu-MOF) with a flower-shaped globular structure was innovatively prepared via self-assembling of α-glucosidase (GAA), glucose oxidase (GOx), Cu²⁺, and 4,4'-bipyridine. It was found that GAA@GOx@Cu-MOF not only enjoyed merits of high stability, selectivity, and sensitivity but also possessed the character of assembly line work, with about 4.58 times enhanced enzyme activity compared with the free enzyme system. Based on the above characteristics, a highly sensitive screening of GAA inhibitors could be achieved with the detection limit of 7.05 nM for acarbose. Furthermore, the proposed method was successfully applied to the screening of oleanolic acid derivatives as potential antidiabetic drugs. Therefore, it was expected that this work could provide new insights and inspirations for the screening of clinical antidiabetic drugs and for further exploration of functional MOF composites.