A1 Refereed original research article in a scientific journal
A molecular container providing supramolecular protection against acetylcholine hydrolysis
Authors: Lu Yi-Long, Su Jing, Li Jian-Wei, Xu Wen-Rong
Publisher: Royal Society of Chemistry
Publication year: 2024
Journal: Organic and Biomolecular Chemistry
Journal name in source: ORGANIC & BIOMOLECULAR CHEMISTRY
Journal acronym: ORG BIOMOL CHEM
Volume: 22
Issue: 8
First page : 1634
Last page: 1638
Number of pages: 5
ISSN: 1477-0520
eISSN: 1477-0539
DOI: https://doi.org/10.1039/d4ob00024b
Web address : https://pubs.rsc.org/en/Content/ArticleLanding/2024/OB/D4OB00024B
Abstract
Alzheimer's disease (AD) is characterized by cognitive decline, often attributed to the deficiency of acetylcholine, which can undergo hydrolysis by acetylcholinesterase (AChE) within the biological milieu. Here, we report a supramolecular strategy that takes advantage of confinement effects to inhibit such a hydrolysis process, shedding some light on AD therapy. A water-soluble and bowl-shaped molecule, hexacarboxylated tribenzotriquinacene (TBTQ-C6), was employed to shield acetylcholine (G1) from enzymatic degradation through host-guest binding interactions. Our study revealed highly efficient host-guest interactions with a binding ratio of 1 : 3, resulting in a significant reduction in acetylcholine hydrolysis from 91.1% to 7.4% in the presence of AChE under otherwise identical conditions. Furthermore, TBTQ-C6 showed potential for attenuating the degradation of butyrylcholine (G2) by butyrylcholinesterase (BChE). The broader implications of this study extend to the potential use of molecular containers in various biochemical and pharmacological applications, opening new avenues for research in the field of neurodegenerative diseases.Utilizing confinement effects, TBTQ-C6 safeguards acetylcholine and butyrylcholine from enzymatic breakdown by AChE and BChE through host-guest interactions.
Alzheimer's disease (AD) is characterized by cognitive decline, often attributed to the deficiency of acetylcholine, which can undergo hydrolysis by acetylcholinesterase (AChE) within the biological milieu. Here, we report a supramolecular strategy that takes advantage of confinement effects to inhibit such a hydrolysis process, shedding some light on AD therapy. A water-soluble and bowl-shaped molecule, hexacarboxylated tribenzotriquinacene (TBTQ-C6), was employed to shield acetylcholine (G1) from enzymatic degradation through host-guest binding interactions. Our study revealed highly efficient host-guest interactions with a binding ratio of 1 : 3, resulting in a significant reduction in acetylcholine hydrolysis from 91.1% to 7.4% in the presence of AChE under otherwise identical conditions. Furthermore, TBTQ-C6 showed potential for attenuating the degradation of butyrylcholine (G2) by butyrylcholinesterase (BChE). The broader implications of this study extend to the potential use of molecular containers in various biochemical and pharmacological applications, opening new avenues for research in the field of neurodegenerative diseases.Utilizing confinement effects, TBTQ-C6 safeguards acetylcholine and butyrylcholine from enzymatic breakdown by AChE and BChE through host-guest interactions.
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