Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Ji, Yonghwan | - |
dc.contributor.author | Lee, Hyuck Jin | - |
dc.contributor.author | Kim, Minjeong | - |
dc.contributor.author | Nam, Geewoo | - |
dc.contributor.author | Lee, Shin Jung C. | - |
dc.contributor.author | Cho, Jaeheung | - |
dc.contributor.author | Park, Cheol-Min | - |
dc.contributor.author | Lim, Mi Hee | - |
dc.date.available | 2017-08-10T08:11:44Z | - |
dc.date.created | 2017-08-09 | - |
dc.date.issued | 2017-06-05 | - |
dc.identifier.issn | 0020-1669 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/4157 | - |
dc.description.abstract | The complexity of Alzheimer’s disease (AD) stems from the inter-relation of multiple pathological factors upon initiation and progression of the disease. To identify the involvement of metal-bound amyloid-β (metal-Aβ) aggregation in AD pathology, among the pathogenic features found in the AD-affected brain, small molecules as chemical tools capable of controlling metal-Aβ aggregation were developed. Herein, we report a new class of 2,2′-bipyridine (bpy) derivatives (1-4) rationally designed to be chemical modulators toward metal-Aβ aggregation over metal-free Aβ analogue. The bpy derivatives were constructed through a rational design strategy employing straightforward structural variations onto the backbone of a metal chelator, bpy: (i) incorporation of an Aβ interacting moiety; (ii) introduction of a methyl group at different positions. The newly prepared bpy derivatives were observed to bind to metal ions [i.e., Cu(II) and Zn(II)] and interact with metal-Aβ over metal-free Aβ to varying degrees. Distinguishable from bpy, the bpy derivatives (1-3) were indicated to noticeably modulate the aggregation pathways of Cu(II)-Aβ and Zn(II)-Aβ over metal-free Aβ. Overall, our studies of the bpy derivatives demonstrate that the alteration of metal binding properties as well as the installation of an Aβ interacting capability onto a metal chelating framework, devised via the rational structure-based design, were able to achieve evident modulating reactivity against metal-Aβ aggregation. Obviating the need for complicated structures, our design approach, presented in this work, could be appropriately utilized for inventing small molecules as chemical tools for studying desired metal-related targets in biological systems. © 2017 American Chemical Society. | - |
dc.publisher | American Chemical Society | - |
dc.title | Strategic Design of 2,2 '-Bipyridine Derivatives to Modulate Metal Amyloid-beta Aggregation | - |
dc.type | Article | - |
dc.identifier.doi | 10.1021/acs.inorgchem.7b00782 | - |
dc.identifier.scopusid | 2-s2.0-85020272501 | - |
dc.identifier.bibliographicCitation | Inorganic Chemistry, v.56, no.11, pp.6695 - 6705 | - |
dc.subject.keywordPlus | 2,2&apos | - |
dc.subject.keywordPlus | Dipyridyl | - |
dc.subject.keywordPlus | A Beta | - |
dc.subject.keywordPlus | Absorption | - |
dc.subject.keywordPlus | Alzheimer&apos | - |
dc.subject.keywordPlus | s Disease (AD) | - |
dc.subject.keywordPlus | Complexes | - |
dc.subject.keywordPlus | Coordination | - |
dc.subject.keywordPlus | Mechanisms | - |
dc.subject.keywordPlus | Peptide | - |
dc.subject.keywordPlus | Small Molecules | - |
dc.subject.keywordPlus | Target | - |
dc.citation.endPage | 6705 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 6695 | - |
dc.citation.title | Inorganic Chemistry | - |
dc.citation.volume | 56 | - |
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