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Park, Cheol-Min
Synthetic & Medicinal Chemistry Lab
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  • Organic synthesis, medicinal chemistry, chemical biology

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Strategic Design of 2,2 '-Bipyridine Derivatives to Modulate Metal Amyloid-beta Aggregation

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dc.contributor.author Ji, Yonghwan ko
dc.contributor.author Lee, Hyuck Jin ko
dc.contributor.author Kim, Munjeong ko
dc.contributor.author Nam, Geewoo ko
dc.contributor.author Lee, Shun Jung C. ko
dc.contributor.author Cho. Jaeheung ko
dc.contributor.author Park, Cheol-Min ko
dc.contributor.author Lim, Mi Hee ko
dc.date.available 2017-06-01T09:19:44Z -
dc.date.created 2017-06-01 ko
dc.date.issued 2017-06 ko
dc.identifier.citation INORGANIC CHEMISTRY, v.56, no.11, pp.6695 - 6705 ko
dc.identifier.issn 0020-1669 ko
dc.identifier.uri https://scholarworks.unist.ac.kr/handle/201301/22010 -
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. ko
dc.language 영어 ko
dc.publisher AMER CHEMICAL SOC ko
dc.title Strategic Design of 2,2 '-Bipyridine Derivatives to Modulate Metal Amyloid-beta Aggregation ko
dc.type ARTICLE ko
dc.identifier.scopusid 2-s2.0-85020272501 ko
dc.identifier.wosid 000402950600073 ko
dc.type.rims ART ko
dc.identifier.doi 10.1021/acs.inorgchem.7b00782 ko
dc.identifier.url http://pubs.acs.org/doi/abs/10.1021/acs.inorgchem.7b00782 ko
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