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DC Field | Value | Language |
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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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