DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Sanghyun | ko |
dc.contributor.author | Zheng, Xueyun | ko |
dc.contributor.author | Krishnamoorthy, Janarthanan | ko |
dc.contributor.author | Savelieff, Masha G. | ko |
dc.contributor.author | Park, Hyun Min | ko |
dc.contributor.author | Brender, Jeffrey R. | ko |
dc.contributor.author | Kim, Jin Hoon | ko |
dc.contributor.author | Derrick, Jeffrey S. | ko |
dc.contributor.author | Kochi, Akiko | ko |
dc.contributor.author | Lee, Hyuck Jin | ko |
dc.contributor.author | Kim, Cheal | ko |
dc.contributor.author | Ramamoorthy, Ayyalusamy | ko |
dc.contributor.author | Bowers, Michael T. | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.date.accessioned | 2018-02-21T06:24:10Z | - |
dc.date.available | 2018-02-21T06:24:10Z | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.issued | 2014-01 | - |
dc.identifier.citation | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.136, no.1, pp.299 - 310 | - |
dc.identifier.issn | 0002-7863 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240291 | - |
dc.description.abstract | Alzheimer's disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-beta (A beta) 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 A beta 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 A beta (metal-A beta) species, suppresses A beta aggregation in vitro, and diminishes toxicity induced by A beta and metal-treated A beta in living cells. Comparison of ML to its structural moieties (i.e., 4-(dimethylamino)phenol (DAP) and (8-aminoquinolin-2-yl)methanol (I)) for reactivity with A beta and metal-A beta suggests the synergy of incorporating structural components for both metal chelation and A beta 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.language | English | - |
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.identifier.wosid | 000329586600053 | - |
dc.identifier.scopusid | 2-s2.0-84892177268 | - |
dc.type.rims | ART | - |
dc.citation.volume | 136 | - |
dc.citation.issue | 1 | - |
dc.citation.beginningpage | 299 | - |
dc.citation.endingpage | 310 | - |
dc.citation.publicationname | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | - |
dc.identifier.doi | 10.1021/ja409801p | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Lee, Sanghyun | - |
dc.contributor.nonIdAuthor | Zheng, Xueyun | - |
dc.contributor.nonIdAuthor | Krishnamoorthy, Janarthanan | - |
dc.contributor.nonIdAuthor | Savelieff, Masha G. | - |
dc.contributor.nonIdAuthor | Park, Hyun Min | - |
dc.contributor.nonIdAuthor | Brender, Jeffrey R. | - |
dc.contributor.nonIdAuthor | Kim, Jin Hoon | - |
dc.contributor.nonIdAuthor | Derrick, Jeffrey S. | - |
dc.contributor.nonIdAuthor | Kochi, Akiko | - |
dc.contributor.nonIdAuthor | Lee, Hyuck Jin | - |
dc.contributor.nonIdAuthor | Kim, Cheal | - |
dc.contributor.nonIdAuthor | Ramamoorthy, Ayyalusamy | - |
dc.contributor.nonIdAuthor | Bowers, Michael T. | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
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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