Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Choi, Jung-Suk
  • Braymer, Joseph J
  • Park, Se Kyung
  • Mustafa, Shaik
  • Chae, Junghyun
  • Lim, Mi Hee
Type
Published Article
Journal
Metallomics : integrated biometal science
Publication Date
Mar 01, 2011
Volume
3
Issue
3
Pages
284–291
Identifiers
DOI: 10.1039/c0mt00077a
PMID: 21210061
Source
Medline
License
Unknown

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.

Report this publication

Statistics

Seen <100 times