期刊
ANALYTICA CHIMICA ACTA
卷 1099, 期 -, 页码 94-102出版社
ELSEVIER
DOI: 10.1016/j.aca.2019.11.042
关键词
Metal-organic framework; Ligand fishing; Pancreatic lipase inhibitor; Prunella vulgaris L
资金
- National Natural Science Foundation of China [81872983]
- Drug Innovation Major Project [2018ZX09711-001-007]
- 111 Project from Ministry of Education of China [B18056]
- State Administration of Foreign Experts Affairs of China [B18056]
In terms of ligand fishing, the amount and the relative activity recovery of enzymes immobilized on magnetic particles and nanoparticles are not preeminent. Therefore, the metal-organic framework (MOF) UiO-66-NH2 was synthesized to immobilize the porcine pancreatic lipase (PPL) via precipitation-cross-linking, and the resulting novel biological matrices named PPL@MOF manifested high PPL loading capacity (98.31 mg/g) and relative activity recovery (104.4%). Moreover, the novel enzyme-MOF composite was applied to screen lipase inhibitors from Prunella vulgaris L. to enrich and improve the techniques of ligand fishing. As a result, 13 lipase ligands were obtained, and 12 compounds were determined by HPLCQ-TOF-MS/MS. All of these ligands were further confirmed to be potential inhibitors through the verification of the activity assay and molecular docking. The proposed approach based on PPL@MOF was superior in terms of abundant protein loading capacity, high enzyme catalytic activity and easy preparation process. Taken together, our newly developed method provided a new platform for efficient discovering bioactive molecules from natural herbs. (C) 2019 Elsevier B.V. All rights reserved.
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