A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
A molecular container providing supramolecular protection against acetylcholine hydrolysis
Tekijät: Lu Yi-Long, Su Jing, Li Jian-Wei, Xu Wen-Rong
Kustantaja: Royal Society of Chemistry
Julkaisuvuosi: 2024
Journal: Organic and Biomolecular Chemistry
Tietokannassa oleva lehden nimi: ORGANIC & BIOMOLECULAR CHEMISTRY
Lehden akronyymi: ORG BIOMOL CHEM
Vuosikerta: 22
Numero: 8
Aloitussivu: 1634
Lopetussivu: 1638
Sivujen määrä: 5
ISSN: 1477-0520
eISSN: 1477-0539
DOI: https://doi.org/10.1039/d4ob00024b
Verkko-osoite: https://pubs.rsc.org/en/Content/ArticleLanding/2024/OB/D4OB00024B
Tiivistelmä
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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