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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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Dual-function triazole-pyridine derivatives as inhibitors of metal-induced amyloid-beta aggregation

Cited 21 times inthomson ciCited 15 times inthomson ci
Title
Dual-function triazole-pyridine derivatives as inhibitors of metal-induced amyloid-beta aggregation
Author
Jones, Michael R.Service, Erin L.Thompson, John R.Wang, Michael C. P.Kimsey, Isaac J.DeToma, Alaina S.Ramamoorthy, AyyalusamyLim, Mi HeeStorr, Tim
Keywords
Alzheimer's disease pathologies; Chemical reagents; In-vitro; Metal chelation; Morpholines; Neuronal toxicity; Propan-1-ol; Reactive oxygen species; Transmission electron microscopy tem
Issue Date
2012-08
Publisher
ROYAL SOC CHEMISTRY
Citation
METALLOMICS, v.4, no.9, pp.910 - 920
Abstract
Dysregulated metal ions are hypothesized to play a role in the aggregation of the amyloid-β (Aβ) peptide, leading to Alzheimer's disease (AD) pathology. In addition to direct effects on Aβ aggregation, both Cu and Fe can catalyze the generation of reactive oxygen species (ROS), possibly contributing to significant neuronal toxicity. Therefore, disruption of metal-Aβ interactions has become a viable strategy for AD therapeutic development. Herein, we report a new series of dual-function triazole-pyridine ligands [4-(2-(4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)ethyl)morpholine (L1), 3-(4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)propan-1-ol (L2), 2-(4-(pyridin-2-yl)- 1H-1,2,3-triazol-1-yl)acetic acid (L3), and 5-(4-(pyridin-2-yl)-1H-1,2,3- triazol-1-yl)pentan-1-amine (L4)] that interact with the Aβ peptide and modulate its aggregation in vitro. Metal chelation and Aβ interaction properties of these molecules were studied by UV-vis, NMR spectroscopy and X-ray crystallography. In addition, turbidity and transmission electron microscopy (TEM) were employed to determine the anti-aggregation properties of L1-L4. All compounds demonstrated an ability to limit metal-induced Aβ aggregation. Overall, our studies suggest the utility of the triazole-pyridine framework in the development of chemical reagents toward inhibitors for metal-triggered Aβ aggregation.
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DOI
10.1039/c2mt20113e
ISSN
1756-5901
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PHY_Journal Papers
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