DC Field | Value | Language |
---|---|---|
dc.contributor.author | Braymer, Joseph J. | ko |
dc.contributor.author | Choi, Jung-Suk | ko |
dc.contributor.author | DeToma, Alaina S. | ko |
dc.contributor.author | Wang, Chen | ko |
dc.contributor.author | Nam, Kisoo | ko |
dc.contributor.author | Kampf, Jeffrey W. | ko |
dc.contributor.author | Ramamoorthy, Ayyalusamy | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.date.accessioned | 2018-02-21T06:25:05Z | - |
dc.date.available | 2018-02-21T06:25:05Z | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.issued | 2011-11 | - |
dc.identifier.citation | INORGANIC CHEMISTRY, v.50, no.21, pp.10724 - 10734 | - |
dc.identifier.issn | 0020-1669 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240316 | - |
dc.description.abstract | Amyloid-beta (A beta) peptides and their metal-associated aggregated states have been implicated in the pathogenesis of Alzheimer's disease (AD). Although the etiology of AD remains uncertain, understanding the role of metal-A beta species could provide insights into the onset and development of the disease. To unravel this, bifunctional small molecules that can specifically target and modulate metal-A beta species have been developed, which could serve as suitable chemical tools for investigating metal-A beta-associated events in AD. Through a rational structure-based design principle involving the incorporation of a metal binding site into the structure of an A beta interacting molecule, we devised stilbene derivatives (L1-a and L1-b) and demonstrated their reactivity toward metal-A beta species. In particular, the dual functions of compounds with different structural features (e.g., with or without a dimethylamino group) were explored by UV-vis, X-ray crystallography, high-resolution 2D NMR, and docking studies. Enhanced bifunctionality of compounds provided greater effects on metal-induced A beta aggregation and neurotoxicity in vitro and in living cells. Mechanistic investigations of the reaction of L1-a and L1-b with Zn2+-A beta species by UV-vis and 2D NMR suggest that metal chelation with ligand and/or metal ligand interaction with the A beta peptide may be driving factors for the observed modulation of metal-A beta aggregation pathways. Overall, the studies presented herein demonstrate the importance of a structure-interaction-reactivity relationship for designing small molecules to target metal-A beta species allowing for the modulation of metal-induced A beta reactivity and neurotoxicity. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Development of Bifunctional Stilbene Derivatives for Targeting and Modulating Metal-Amyloid-beta Species | - |
dc.type | Article | - |
dc.identifier.wosid | 000296303900036 | - |
dc.identifier.scopusid | 2-s2.0-80155213679 | - |
dc.type.rims | ART | - |
dc.citation.volume | 50 | - |
dc.citation.issue | 21 | - |
dc.citation.beginningpage | 10724 | - |
dc.citation.endingpage | 10734 | - |
dc.citation.publicationname | INORGANIC CHEMISTRY | - |
dc.identifier.doi | 10.1021/ic2012205 | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Braymer, Joseph J. | - |
dc.contributor.nonIdAuthor | Choi, Jung-Suk | - |
dc.contributor.nonIdAuthor | DeToma, Alaina S. | - |
dc.contributor.nonIdAuthor | Wang, Chen | - |
dc.contributor.nonIdAuthor | Nam, Kisoo | - |
dc.contributor.nonIdAuthor | Kampf, Jeffrey W. | - |
dc.contributor.nonIdAuthor | Ramamoorthy, Ayyalusamy | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | WATER-MICELLE ENVIRONMENT | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | A-BETA | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | BINDING SURFACE | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordPlus | ZINC-BINDING | - |
dc.subject.keywordPlus | PEPTIDE | - |
dc.subject.keywordPlus | NMR | - |
dc.subject.keywordPlus | AGGREGATION | - |
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