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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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Synthesis and characterization of IMPY derivatives that regulate metal-induced amyloid-beta aggregation

Cited 22 times inthomson ciCited 18 times inthomson ci
Title
Synthesis and characterization of IMPY derivatives that regulate metal-induced amyloid-beta aggregation
Author
Choi, Jung-SukBraymer, Joseph J.Park, Se KyungMustafa, ShaikChae, JunghyunLim, Mi Hee
Keywords
Alzheimer's disease; Bifunctional; Design strategies; Disaggregation; High resolution; In-vitro; Metal chelation; Metal-free conditions; Neurodegeneration; Small molecules; Structure-based
Issue Date
2011
Publisher
ROYAL SOC CHEMISTRY
Citation
METALLOMICS, v.3, no.3, pp.284 - 291
Abstract
Metal ions associated with amyloid-β (Aβ) species have been suggested to be involved in neurodegeneration leading to the progression of Alzheimer's disease (AD). The role of metal-involved Aβ species in AD neuropathogenesis, however, is not fully elucidated. In order to advance this understanding and contribute to the therapeutic development for AD, the rational structure-based design of small molecules that specifically target metal ions surrounded by Aβ species has recently received increased attention. To date, only a few compounds have been fashioned for this purpose. Herein, we report the design strategy, synthesis, characterization, and reactivity of new bifunctional IMPY derivatives K1 and K2. Using UV-vis and high-resolution two-dimensional (2D) NMR spectroscopy, the bifunctionality of K1 and K2 (metal chelation and Aβ interaction) was confirmed. These bifunctional IMPY derivatives showed preferential reactivity toward metal-induced Aβ aggregation over metal-free conditions in both in vitro inhibition and disaggregation experiments. Taken together, this study provides another example of a bifunctional small molecule framework that can target metal ions associated with Aβ species.
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DOI
10.1039/c0mt00077a
ISSN
1756-5901
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PHY_Journal Papers
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