There are no files associated with this item.
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.citation.endPage | 5167 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 5160 | - |
dc.citation.title | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.volume | 117 | - |
dc.contributor.author | Han, Jiyeon | - |
dc.contributor.author | Lee, Hyuck Jin | - |
dc.contributor.author | Kim, Kyu Yeon | - |
dc.contributor.author | Nam, Geewoo | - |
dc.contributor.author | Chae, Junghyun | - |
dc.contributor.author | Lim, Mi Hee | - |
dc.date.accessioned | 2023-12-21T17:48:42Z | - |
dc.date.available | 2023-12-21T17:48:42Z | - |
dc.date.created | 2020-04-02 | - |
dc.date.issued | 2020-03 | - |
dc.description.abstract | Neurotoxic implications of the interactions between Cu(I/II) and amyloid-beta (A beta) indicate a connection between amyloid cascade hypothesis and metal ion hypothesis with respect to the neurodegeneration associated with Alzheimer's disease (AD). Herein, we report a mechanistic strategy for modifying the first coordination sphere of Cu(II) bound to A beta utilizing a rationally designed peptide modifier, L1. Upon reacting with L1, a metal-binding histidine (His) residue, His14, in Cu(II)-A beta was modified through either covalent adduct formation, oxidation, or both. Consequently, the reactivity of L1 with Cu(II)-A beta was able to disrupt binding of Cu(II) to A beta and result in chemically modified A beta with altered aggregation and toxicity profiles. Our molecular-level mechanistic studies revealed that such L1-mediated modifications toward Cu(II)-A beta could stem from the molecule's ability to 1) interact with Cu(II)A beta and 2) foster copper-O-2 chemistry. Collectively, our work demonstrates the development of an effective approach to modify Cu(II)-A beta at a metal-binding amino acid residue and consequently alter A beta's coordination to copper, aggregation, and toxicity, supplemented with an in-depth mechanistic perspective regarding such reactivity. | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.117, no.10, pp.5160 - 5167 | - |
dc.identifier.doi | 10.1073/pnas.1916944117 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.scopusid | 2-s2.0-85081695543 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/31882 | - |
dc.identifier.url | https://www.pnas.org/content/117/10/5160 | - |
dc.identifier.wosid | 000519530400017 | - |
dc.language | 영어 | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.title | Mechanistic approaches for chemically modifying the coordination sphere of copper-amyloid-beta complexes | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | copper | - |
dc.subject.keywordAuthor | amyloid-beta | - |
dc.subject.keywordAuthor | small molecule | - |
dc.subject.keywordAuthor | copper-O-2 chemistry | - |
dc.subject.keywordAuthor | residue-specific modifications | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | MASS-SPECTROMETRY | - |
dc.subject.keywordPlus | METAL-IONS | - |
dc.subject.keywordPlus | PEPTIDES | - |
dc.subject.keywordPlus | CHEMISTRY | - |
dc.subject.keywordPlus | OXIDATION | - |
dc.subject.keywordPlus | AGGREGATION | - |
dc.subject.keywordPlus | OLIGOMERS | - |
dc.subject.keywordPlus | MOLECULE | - |
dc.subject.keywordPlus | HOMEOSTASIS | - |
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Tel : 052-217-1404 / Email : scholarworks@unist.ac.kr
Copyright (c) 2023 by UNIST LIBRARY. All rights reserved.
ScholarWorks@UNIST was established as an OAK Project for the National Library of Korea.