Bifunctional Hybrid Enzyme-Catalytic Metal Organic Framework Reactor for α-glucosidase Inhibitor Screening.

The screening strategy based on α-glucosidase inhibition has been widely employed for the discovery of anti-diabetic 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 anti-diabetic drugs. Therefore, it was expected that this work could provide new insights and inspirations for the screening of clinical anti-diabetic drugs and for further exploration of functional MOF composites.