DC Field | Value | Language |
---|---|---|
dc.contributor.author | Derrick, Jeffrey S. | ko |
dc.contributor.author | Kerr, Richard A. | ko |
dc.contributor.author | Nam, Younwoo | ko |
dc.contributor.author | Oh, Shin Bi | ko |
dc.contributor.author | Lee, Hyuck Jin | ko |
dc.contributor.author | Earnest, Kaylin G. | ko |
dc.contributor.author | Suh, Nayoung | ko |
dc.contributor.author | Peck, Kristy L. | ko |
dc.contributor.author | Ozbil, Mehmet | ko |
dc.contributor.author | Korshavn, Kyle J. | ko |
dc.contributor.author | Ramamoorthy, Ayyalusamy | ko |
dc.contributor.author | Prabhakar, Rajeev | ko |
dc.contributor.author | Merino, Edward J. | ko |
dc.contributor.author | Shearer, Jason | ko |
dc.contributor.author | Lee, Joo-Yong | ko |
dc.contributor.author | Ruotolo, Brandon T. | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.date.accessioned | 2018-02-21T06:06:23Z | - |
dc.date.available | 2018-02-21T06:06:23Z | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.issued | 2015-11 | - |
dc.identifier.citation | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.137, no.46, pp.14785 - 14797 | - |
dc.identifier.issn | 0002-7863 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240281 | - |
dc.description.abstract | Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. Herein, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-beta (A beta) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligandpeptide adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimers disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble A beta forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Overall, our in vitro and in vivo studies of DMPD toward A beta with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms | - |
dc.type | Article | - |
dc.identifier.wosid | 000366004700032 | - |
dc.identifier.scopusid | 2-s2.0-84948664618 | - |
dc.type.rims | ART | - |
dc.citation.volume | 137 | - |
dc.citation.issue | 46 | - |
dc.citation.beginningpage | 14785 | - |
dc.citation.endingpage | 14797 | - |
dc.citation.publicationname | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | - |
dc.identifier.doi | 10.1021/jacs.5b10043 | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Derrick, Jeffrey S. | - |
dc.contributor.nonIdAuthor | Kerr, Richard A. | - |
dc.contributor.nonIdAuthor | Nam, Younwoo | - |
dc.contributor.nonIdAuthor | Oh, Shin Bi | - |
dc.contributor.nonIdAuthor | Lee, Hyuck Jin | - |
dc.contributor.nonIdAuthor | Earnest, Kaylin G. | - |
dc.contributor.nonIdAuthor | Suh, Nayoung | - |
dc.contributor.nonIdAuthor | Peck, Kristy L. | - |
dc.contributor.nonIdAuthor | Ozbil, Mehmet | - |
dc.contributor.nonIdAuthor | Korshavn, Kyle J. | - |
dc.contributor.nonIdAuthor | Ramamoorthy, Ayyalusamy | - |
dc.contributor.nonIdAuthor | Prabhakar, Rajeev | - |
dc.contributor.nonIdAuthor | Merino, Edward J. | - |
dc.contributor.nonIdAuthor | Shearer, Jason | - |
dc.contributor.nonIdAuthor | Lee, Joo-Yong | - |
dc.contributor.nonIdAuthor | Ruotolo, Brandon T. | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | NEURODEGENERATIVE DISEASES | - |
dc.subject.keywordPlus | MASS SPECTROMETRY | - |
dc.subject.keywordPlus | BETA AGGREGATION | - |
dc.subject.keywordPlus | BINDING-SITE | - |
dc.subject.keywordPlus | METAL-IONS | - |
dc.subject.keywordPlus | COMPLEXES | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | PATHOGENESIS | - |
dc.subject.keywordPlus | ENVIRONMENT | - |
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