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

Abstract

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), Cu 2+ , 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.

Metal–Organic Frameworks Enhance Biomimetic Cascade Catalysis for Biosensing

“…d–f) Reproduced with permission. [ 107 ] Copyright 2019, American Chemical Society. g) Schematic about the cascade catalysis for electrochemical monitoring of CA15‐3.…”

“…e) The storage stability and f) thermal stability of GAA@GOx and GAA@GOx@Cu-MOF. d-f) Reproduced with permission [107]. Copyright 2019, American Chemical Society.…”

Biocatalytic Metal–Organic Frameworks: Prospects Beyond Bioprotective Porous Matrices

“…[90,91] Gold nanorods AuNRs/enzyme/ZIF-8 retained 85% enzymatic activity after exposure to 55 o C for 7 d. [92] Graphene oxide Cyt c@ZIF-8/GO showed enhanced organic solvents and storage stability. cells/mL 6 cells/mL [39] ZIF-8 Cu-MOF GAA and GOx Maltose Colorimetric 12.5-800 μM 7.05 nM [38] ZIF-8 GOx Glucose Waveguide 1-8 mM -- [37] Tb-BTC OPH 6His Methyl parathion UV-vis absorbance 10-10 6 ng/mL 2.6 nM [43] UiO-66-…”

Review of the Biomolecular Modification of the Metal-Organ-Framework

“…The framework could effectively maintain the skeletal integrity, biological activity, and reusability of proteins (Cao et al, 2016 ). It was reported that two enzymes, α-glucosidase (GAA) and glucose oxidase (GOx), could be assembled on one Cu-MOF molecule to generate a bifunctional hybrid enzyme-catalytic framework reactor, which could be utilized for the highly sensitive and stable screening of GAA inhibitors (Zhong et al, 2019 ). In terms of nucleic acids, low-molecular weight (MW) molecules such as oligonucleotide CpG ODNs (Zhang et al, 2017 ) and ssDNA (11, 22, 33, and 53 nucleotides) (Peng et al, 2018 ) have been wrapped and combined with MOFs.…”