Visual screening of butyrylcholinesterase inhibitors by a cellulose membrane biosensor with amide-bonded immobilization of butyrylcholinesterase in a solid-phase enzyme-catalyzed reaction

Int J Biol Macromol. 2025 Jan:285:138598. doi: 10.1016/j.ijbiomac.2024.138598. Epub 2024 Dec 9.

Abstract

The rapid discovery of highly active butyrylcholinesterase (BChE) inhibitors is key to the treatment of the late stages of Alzheimer's disease. Herein, a colorimetric cellulose membrane (CM)-based biosensor was developed. The CM was employed as a carrier, which can be immobilized with the BChE and 5,5'-dithio-(2-nitrobenzoic acid) (DTNB) to prepare the biosensor for the solid-phase enzyme-catalyzed reaction. Specifically, the CM was oxidized to the oxidized cellulose membrane (OCM), which can further covalently bind the BChE to prepare the BChE-immobilized cellulose membrane (BCM). Then, the DTNB was adsorbed to the BCM to prepare the BDCM biosensor. The BDCM biosensor can visually detect S-butyrylthiocholine iodide at the yellow light signal with several characters, including sensitivity (LOD 1.56 μM), affinity (Km = 140.48 ± 5.42 μM), stability (over 1 month), via the BChE-catalyzed solid-phase reaction. Furthermore, the BDCM biosensor was applied to screen and determine the specific commercial BChE inhibitors tacrine and rivastigmine, with the IC50 values of 30.99 ± 12.20 nM and 2.02 ± 0.13 μM, respectively, from 13 different commercial inhibitors. This work provided a new method of visual BChE inhibitor screening and a useful strategy for the design of enzyme-based immobilization technology cellulose membrane biosensors.

Keywords: Biosensor; Butyrylcholinesterase; Cellulose membrane.

MeSH terms

  • Amides / chemistry
  • Biosensing Techniques* / methods
  • Butyrylcholinesterase* / chemistry
  • Butyrylcholinesterase* / metabolism
  • Cellulose* / analogs & derivatives
  • Cellulose* / chemistry
  • Cholinesterase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / pharmacology
  • Enzymes, Immobilized* / chemistry
  • Enzymes, Immobilized* / metabolism
  • Humans
  • Membranes, Artificial*
  • Tacrine / chemistry

Substances

  • Butyrylcholinesterase
  • Cellulose
  • Enzymes, Immobilized
  • Cholinesterase Inhibitors
  • Membranes, Artificial
  • Amides
  • Tacrine