guest ::
| Home > Publications database > Discovery and structure activity relationship of small molecule inhibitors of toxic-ß--amyloid-42 fibril formation |
| Home > Publications database > Discovery and structure activity relationship of small molecule inhibitors of toxic-ß--amyloid-42 fibril formation |
| Journal Article | PreJuSER-23050 |
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
2012
Soc.
Bethesda, Md.
This record in other databases: 
Please use a persistent id in citations: doi:10.1074/jbc.M112.357665
Abstract: Increasing evidence implicates Aβ peptides self-assembly and fibril formation as crucial events in the pathogenesis of Alzheimer disease. Thus, inhibiting Aβ aggregation, among others, has emerged as a potential therapeutic intervention for this disorder. Herein, we employed 3-aminopyrazole as a key fragment in our design of non-dye compounds capable of interacting with Aβ42 via a donor-acceptor-donor hydrogen bond pattern complementary to that of the β-sheet conformation of Aβ42. The initial design of the compounds was based on connecting two 3-aminopyrazole moieties via a linker to identify suitable scaffold molecules. Additional aryl substitutions on the two 3-aminopyrazole moieties were also explored to enhance π-π stacking/hydrophobic interactions with amino acids of Aβ42. The efficacy of these compounds on inhibiting Aβ fibril formation and toxicity in vitro was assessed using a combination of biophysical techniques and viability assays. Using structure activity relationship data from the in vitro assays, we identified compounds capable of preventing pathological self-assembly of Aβ42 leading to decreased cell toxicity.
; BIOSIS Previews ; Current Contents - Life Sciences ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
|
The record appears in these collections: |
