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Lim, Mi Hee
MetalloNeuroChemistry Lab (MNCL)
Research Interests
  • Neurodegenerative disease, small molecule design, network between metal, proteins, and ROS

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Small Molecule Modulators of Copper-Induced A beta Aggregation

Cited 91 times inthomson ciCited 90 times inthomson ci
Title
Small Molecule Modulators of Copper-Induced A beta Aggregation
Author
Hindo, Sarmad S.Mancino, Allana M.Braymer, Joseph J.Liu, YihongVivekanandan, SubramanianRamamoorthy, AyyalusamyLim, Mi Hee
Keywords
Alzheimer's disease; Bifunctional; Chelating agent; Chemical equations; Chemical probes; Chemical tools; Imaging agent; Metal binding; Metal chelation; Metal chelator; Metal-ion chelation; Multi-functional molecules; Small molecules; Spectroscopic method; Structural frameworks; Therapeutic agents
Issue Date
2009-11
Publisher
AMER CHEMICAL SOC
Citation
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.131, no.46, pp.16663 - 16665
Abstract
(Chemical Equation Presented) Our design of bifunctional metal chelators as chemical probes and potential therapeutics for Alzheimer's disease (AD) is based on the incorporation of a metal binding moiety into structural frameworks of Aβ aggregate-imaging agents. Using this strategy, two compounds 2-[4-(dimethylamino)phenyl]imidazo[1,2-a]pyridine-8-ol (1) and N 1,N1-dimethyl-N4-(pyridin-2-ylmethylene) benzene-1,4-diamine (2) were prepared and characterized. The bifunctionality for metal chelation and Aβ interaction of 1 and 2 was verified by spectroscopic methods. Furthermore, the reactivity of 1 and 2 with Cu II-associated Aβ aggregates was investigated. The modulation of CuII-triggered Aβ aggregation by 1 and 2 was found to be more effective than that by the known metal chelating agents CQ, EDTA, and phen. These studies suggest a new class of multifunctional molecules for the development of chemical tools to unravel metal-associated events in AD and potential therapeutic agents for metal-ion chelation therapy.
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DOI
10.1021/ja907045h
ISSN
0002-7863
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PHY_Journal Papers
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