DC Field | Value | Language |
---|---|---|
dc.contributor.author | Han, Jiyeon | ko |
dc.contributor.author | Lee, Hyuck Jin | ko |
dc.contributor.author | Kim, Kyu Yeon | ko |
dc.contributor.author | Nam, Geewoo | ko |
dc.contributor.author | Chae, Junghyun | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.date.accessioned | 2020-04-09T07:20:09Z | - |
dc.date.available | 2020-04-09T07:20:09Z | - |
dc.date.created | 2020-03-30 | - |
dc.date.created | 2020-03-30 | - |
dc.date.issued | 2020-03 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.117, no.10, pp.5160 - 5167 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10203/273850 | - |
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.language | English | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.title | Mechanistic approaches for chemically modifying the coordination sphere of copper-amyloid-beta complexes | - |
dc.type | Article | - |
dc.identifier.wosid | 000519530400017 | - |
dc.identifier.scopusid | 2-s2.0-85081695543 | - |
dc.type.rims | ART | - |
dc.citation.volume | 117 | - |
dc.citation.issue | 10 | - |
dc.citation.beginningpage | 5160 | - |
dc.citation.endingpage | 5167 | - |
dc.citation.publicationname | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.identifier.doi | 10.1073/pnas.1916944117 | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Lee, Hyuck Jin | - |
dc.contributor.nonIdAuthor | Kim, Kyu Yeon | - |
dc.contributor.nonIdAuthor | Nam, Geewoo | - |
dc.contributor.nonIdAuthor | Chae, Junghyun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
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 | - |
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