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dc.citation.endPage 310 -
dc.citation.number 1 -
dc.citation.startPage 299 -
dc.citation.title JOURNAL OF THE AMERICAN CHEMICAL SOCIETY -
dc.citation.volume 136 -
dc.contributor.author Lee, Sanghyun -
dc.contributor.author Zheng, Xueyun -
dc.contributor.author Krishnamoorthy, Janarthanan -
dc.contributor.author Savelieff, Masha G. -
dc.contributor.author Park, Hyun Min -
dc.contributor.author Brender, Jeffrey R. -
dc.contributor.author Kim, Jin Hoon -
dc.contributor.author Derrick, Jeffrey S. -
dc.contributor.author Kochi, Akiko -
dc.contributor.author Lee, Hyuck Jin -
dc.contributor.author Kim, Cheal -
dc.contributor.author Ramamoorthy, Ayyalusamy -
dc.contributor.author Bowers, Michael T. -
dc.contributor.author Lim, Mi Hee -
dc.date.accessioned 2023-12-22T03:08:39Z -
dc.date.available 2023-12-22T03:08:39Z -
dc.date.created 2014-01-24 -
dc.date.issued 2014-01 -
dc.description.abstract Alzheimer’s disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-β (Aβ) aggregation, metal ion dyshomeostasis, and oxidative stress. We report a novel compound (ML) prototype of a rationally designed molecule obtained by integrating structural elements for Aβ aggregation control, metal chelation, reactive oxygen species (ROS) regulation, and antioxidant activity within a single molecule. Chemical, biochemical, ion mobility mass spectrometric, and NMR studies indicate that the compound ML targets metal-free and metal-bound Aβ (metal-Aβ) species, suppresses Aβ aggregation in vitro, and diminishes toxicity induced by Aβ and metal-treated Aβ in living cells. Comparison of ML to its structural moieties (i.e., 4-(dimethylamino)phenol (DAP) and (8-aminoquinolin-2-yl)methanol (1)) for reactivity with Aβ and metal-Aβ suggests the synergy of incorporating structural components for both metal chelation and Aβ interaction. Moreover, ML is water-soluble and potentially brain permeable, as well as regulates the formation and presence of free radicals. Overall, we demonstrate that a rational structure-based design strategy can generate a small molecule that can target and modulate multiple factors, providing a new tool to uncover and address AD complexity. -
dc.identifier.bibliographicCitation JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.136, no.1, pp.299 - 310 -
dc.identifier.doi 10.1021/ja409801p -
dc.identifier.issn 0002-7863 -
dc.identifier.scopusid 2-s2.0-84892177268 -
dc.identifier.uri https://scholarworks.unist.ac.kr/handle/201301/3865 -
dc.identifier.url http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84892177268 -
dc.identifier.wosid 000329586600053 -
dc.language 영어 -
dc.publisher AMER CHEMICAL SOC -
dc.title Rational design of a structural framework with potential use to develop chemical reagents that target and modulate multiple facets of Alzheimer's disease -
dc.type Article -
dc.description.isOpenAccess FALSE -
dc.relation.journalWebOfScienceCategory Chemistry, Multidisciplinary -
dc.relation.journalResearchArea Chemistry -
dc.description.journalRegisteredClass scie -
dc.description.journalRegisteredClass scopus -
dc.subject.keywordPlus AMYLOID-BETA-PROTEIN -
dc.subject.keywordPlus DIPHENYLPROPYNONE DERIVATIVES -
dc.subject.keywordPlus NMR-SPECTROSCOPY -
dc.subject.keywordPlus ATOMIC CHARGES -
dc.subject.keywordPlus GAS-PHASE -
dc.subject.keywordPlus AGGREGATION -
dc.subject.keywordPlus PEPTIDE -
dc.subject.keywordPlus MOLECULES -
dc.subject.keywordPlus BINDING -
dc.subject.keywordPlus OLIGOMERIZATION -

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