Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor
Identifieur interne : 000391 ( Main/Exploration ); précédent : 000390; suivant : 000392Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor
Auteurs : Shengke Li [République populaire de Chine] ; Huanxian Chen [République populaire de Chine] ; Xue Yang [République populaire de Chine] ; David Bardelang [France] ; Ian W. Wyman [Canada] ; Jianbo Wan [République populaire de Chine] ; Simon M. Y. Lee [République populaire de Chine] ; Ruibing Wang [République populaire de Chine]Source :
- ACS Medicinal Chemistry Letters [ 1948-5875 ] ; 2015-12-10.
English descriptors
Abstract
Cucurbit[7]uril (CB[7]) was found in vitro to sequester the neurotoxins MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ (N-methyl-4-phenylpyridine). The CB[7]/neurotoxin host–guest complexes were studied in detail with 1H NMR, electrospray ionization mass spectrometry, UV–visible spectroscopic titration, and molecular modeling by density functional theory. The results supported the macrocyclic encapsulation of MPTP and MPP+, respectively, by CB[7] in aqueous solutions with relatively strong affinities and 1:1 host–guest binding stoichiometries in both cases. More importantly, the progression of MPTP/MPP+ induced neurodegeneration (often referred to as a Parkinson’s disease model) was observed to be strongly inhibited in vivo by the synthetic CB[7] receptor, as shown in zebrafish models. These results show that a supramolecular approach could lead to a new preventive and/or therapeutic strategy for counteracting the deleterious effects of some neurotoxins leading to neurodegeneration.
Url:
DOI: 10.1021/acsmedchemlett.5b00372
Affiliations:
- Canada, France, République populaire de Chine
- Provence-Alpes-Côte d'Azur
- Marseille
- Université d'Aix-Marseille
Links toward previous steps (curation, corpus...)
- to stream Hal, to step Corpus: 000A70
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- to stream Hal, to step Checkpoint: 000118
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- to stream Main, to step Curation: 000391
Le document en format XML
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S" first="Shengke" last="Li">Shengke Li</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-475782" status="INCOMING"> <orgName>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China</orgName> <desc> <address> <country key="CN"></country> </address> </desc> <listRelation> <relation active="#struct-475781" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-475781" type="direct"><org type="institution" xml:id="struct-475781" status="INCOMING"> <orgName>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China</orgName> <desc> <address> <country key="CN"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>République populaire de Chine</country></affiliation></author><author><name sortKey="Chen, Huanxian" sort="Chen, Huanxian" 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Wyman</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-261403" status="INCOMING"> <orgName>Chemistry Department, Queen's University</orgName> <desc> <address> <addrLine>Kingston, Ontario, Canada K7L 3N6</addrLine> <country key="CA"></country> </address> </desc> <listRelation> <relation active="#struct-300659" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-300659" type="direct"><org type="institution" xml:id="struct-300659" status="VALID"> <orgName>Queen's University, Kingston, Ontario</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Canada</country></affiliation></author><author><name sortKey="Wan, Jianbo" sort="Wan, Jianbo" uniqKey="Wan J" first="Jianbo" last="Wan">Jianbo Wan</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-475782" status="INCOMING"> <orgName>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China</orgName> <desc> <address> <country key="CN"></country> </address> </desc> <listRelation> <relation active="#struct-475781" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-475781" type="direct"><org type="institution" xml:id="struct-475781" status="INCOMING"> <orgName>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China</orgName> <desc> <address> <country key="CN"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>République populaire de Chine</country></affiliation></author><author><name sortKey="Lee, Simon M Y" sort="Lee, Simon M Y" uniqKey="Lee S" first="Simon M. Y." last="Lee">Simon M. Y. Lee</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-475782" status="INCOMING"> <orgName>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China</orgName> <desc> <address> <country key="CN"></country> </address> </desc> <listRelation> <relation active="#struct-475781" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-475781" type="direct"><org type="institution" xml:id="struct-475781" status="INCOMING"> <orgName>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China</orgName> <desc> <address> <country key="CN"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>République populaire de Chine</country></affiliation></author><author><name sortKey="Wang, Ruibing" sort="Wang, Ruibing" uniqKey="Wang R" first="Ruibing" last="Wang">Ruibing Wang</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-475782" status="INCOMING"> <orgName>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China</orgName> <desc> <address> <country key="CN"></country> </address> </desc> <listRelation> <relation active="#struct-475781" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-475781" type="direct"><org type="institution" xml:id="struct-475781" status="INCOMING"> <orgName>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China</orgName> <desc> <address> <country key="CN"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>République populaire de Chine</country></affiliation></author></analytic><idno type="DOI">10.1021/acsmedchemlett.5b00372</idno><series><title level="j">ACS Medicinal Chemistry Letters</title><idno type="ISSN">1948-5875</idno><imprint><date type="datePub">2015-12-10</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term> Neurodegeneration</term><term> cucurbituril</term><term> inhibition</term><term> neurotoxin</term><term> supramolecular complexation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cucurbit[7]uril (CB[7]) was found in vitro to sequester the neurotoxins MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ (N-methyl-4-phenylpyridine). The CB[7]/neurotoxin host–guest complexes were studied in detail with 1H NMR, electrospray ionization mass spectrometry, UV–visible spectroscopic titration, and molecular modeling by density functional theory. The results supported the macrocyclic encapsulation of MPTP and MPP+, respectively, by CB[7] in aqueous solutions with relatively strong affinities and 1:1 host–guest binding stoichiometries in both cases. More importantly, the progression of MPTP/MPP+ induced neurodegeneration (often referred to as a Parkinson’s disease model) was observed to be strongly inhibited in vivo by the synthetic CB[7] receptor, as shown in zebrafish models. These results show that a supramolecular approach could lead to a new preventive and/or therapeutic strategy for counteracting the deleterious effects of some neurotoxins leading to neurodegeneration.</div></front></TEI><affiliations><list><country><li>Canada</li><li>France</li><li>République populaire de Chine</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement><orgName><li>Université d'Aix-Marseille</li></orgName></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Li, Shengke" sort="Li, Shengke" uniqKey="Li S" first="Shengke" last="Li">Shengke Li</name></noRegion><name sortKey="Chen, Huanxian" sort="Chen, Huanxian" uniqKey="Chen H" first="Huanxian" last="Chen">Huanxian Chen</name><name sortKey="Lee, Simon M Y" sort="Lee, Simon M Y" uniqKey="Lee S" first="Simon M. Y." last="Lee">Simon M. Y. Lee</name><name sortKey="Wan, Jianbo" sort="Wan, Jianbo" uniqKey="Wan J" first="Jianbo" last="Wan">Jianbo Wan</name><name sortKey="Wang, Ruibing" sort="Wang, Ruibing" uniqKey="Wang R" first="Ruibing" last="Wang">Ruibing Wang</name><name sortKey="Yang, Xue" sort="Yang, Xue" uniqKey="Yang X" first="Xue" last="Yang">Xue Yang</name></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Bardelang, David" sort="Bardelang, David" uniqKey="Bardelang D" first="David" last="Bardelang">David Bardelang</name></region></country><country name="Canada"><noRegion><name sortKey="Wyman, Ian W" sort="Wyman, Ian W" uniqKey="Wyman I" first="Ian W." last="Wyman">Ian W. Wyman</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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