File Download

There are no files associated with this item.

  • Find it @ UNIST can give you direct access to the published full text of this article. (UNISTARs only)

Views & Downloads

Detailed Information

Cited time in webofscience Cited time in scopus
Metadata Downloads

Reactivity of Diphenylpropynone Derivatives Toward Metal-Associated Amyloid-beta Species

Author(s)
Pithadia, Amit S.Kochi, AkikoSoper, Molly T.Beck, Michael W.Liu, YuzhongLee, SanghyunDeToma, Alaina S.Ruotolo, Brandon T.Lim, Mi Hee
Issued Date
2012-12
DOI
10.1021/ic302084g
URI
https://scholarworks.unist.ac.kr/handle/201301/8614
Fulltext
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84870541207
Citation
INORGANIC CHEMISTRY, v.51, no.23, pp.12959 - 12967
Abstract
In Alzheimer's disease (AD), metal-associated amyloid-β (metal-Aβ) species have been suggested to be involved in neurotoxicity; however, their role in disease development is still unclear. To elucidate this aspect, chemical reagents have been developed as valuable tools for targeting metal-Aβ species, modulating the interaction between the metal and Aβ, and subsequently altering metal-Aβ reactivity. Herein, we report the design, preparation, characterization, and reactivity of two diphenylpropynone derivatives (DPP1 and DPP2) composed of structural moieties for metal chelation and Aβ interaction (bifunctionality). The interactions of these compounds with metal ions and Aβ species were confirmed by UV-vis, NMR, mass spectrometry, and docking studies. The effects of these bifunctional molecules on the control of in vitro metal-free and metal-induced Aβ aggregation were investigated and monitored by gel electrophoresis and transmission electron microscopy (TEM). Both DPP1 and DPP2 showed reactivity toward metal-Aβ species over metal-free Aβ species to different extents. In particular, DPP2, which contains a dimethylamino group, exhibited greater reactivity with metal-Aβ species than DPP1, suggesting a structure-reactivity relationship. Overall, our studies present a new bifunctional scaffold that could be utilized to develop chemical reagents for investigating metal-Aβ species in AD.
Publisher
AMER CHEMICAL SOC
ISSN
0020-1669
Keyword
ALZHEIMERS-DISEASENEURODEGENERATIVE DISEASESMASS-SPECTROMETRYOXIDATIVE STRESSAGGREGATIONBINDINGCOPPERZINCPERMEABILITYPROGRAM

qrcode

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.