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In vivo visualization of enantioselective targeting of amyloid and improvement of cognitive function by clickable chiral metallohelices
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Du, Zhi, Liu, Chun, Liu, Zhenqi, Song, Hualong, Scott, Peter, Du, Xiubo, Ren, Jinsong and Qu, Xiaogang (2023) In vivo visualization of enantioselective targeting of amyloid and improvement of cognitive function by clickable chiral metallohelices. Chemical Science, 14 (3). pp. 506-513. doi:10.1039/d2sc05897a ISSN 2041-6520.
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Official URL: http://doi.org/10.1039/d2sc05897a
Abstract
The pathogenesis of Alzheimer's disease (AD) is closely related to several contributing factors, especially amyloid-β (Aβ) aggregation. Bioorthogonal reactions provide a general, facile, and robust route for the localization and derivatization of Aβ-targeted agents. Herein, a pair of chiral alkyne-containing metallohelices (ΛA and ΔA) were demonstrated to enantioselectively target and modulate Aβ aggregation, which has been monitored in triple-transgenic AD model mice and proved to improve cognitive function. Compared with its enantiomer ΔA, ΛA performed better in blocking Aβ fibrillation, relieving Aβ-triggered toxicity, and recovering memory deficits in vivo. Moreover, clickable ΛA could act as a functional module for subsequent visualization and versatile modification of amyloid via bioorthogonal reaction. As a proof-of-concept, thioflavin T, tacrine, and magnetic nanoparticles were conjugated with ΛA to realize Aβ photo-oxygenation, acetylcholinesterase inhibition, and Aβ clearance, respectively. This proof-of-principle work provided new insights into the biolabeling and bioconjugation of multifunctional metallosupramolecules through click reactions for AD therapy.
Item Type: | Journal Article | ||||||||||||||||||
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Subjects: | Q Science > QD Chemistry R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Alzheimer's disease, Alzheimer's disease -- Pathophysiology, Amyloid beta-protein -- Physiology, Organometallic compounds -- Synthesis | ||||||||||||||||||
Journal or Publication Title: | Chemical Science | ||||||||||||||||||
Publisher: | Royal Society of Chemistry | ||||||||||||||||||
ISSN: | 2041-6520 | ||||||||||||||||||
Official Date: | 21 January 2023 | ||||||||||||||||||
Dates: |
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Volume: | 14 | ||||||||||||||||||
Number: | 3 | ||||||||||||||||||
Page Range: | pp. 506-513 | ||||||||||||||||||
DOI: | 10.1039/d2sc05897a | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
Date of first compliant deposit: | 7 February 2023 | ||||||||||||||||||
Date of first compliant Open Access: | 7 February 2023 | ||||||||||||||||||
RIOXX Funder/Project Grant: |
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