Effects of peptides derived from terminal modifications of the aβ central hydrophobic core on aβ fibrillization.

ABSTRACT: Considerable research effort has focused on the discovery of mitigators that block the toxicity of the β-amyloid peptide (Aβ) by targeting a specific step involved in Aβ fibrillogenesis and subsequent aggregation. Given that aggregation intermediates are hypothesized to be responsible for Aβ toxicity, such compounds could likely prevent or mitigate aggregation, or alternatively cause further association of toxic oligomers into larger nontoxic aggregates. Herein we investigate the effect of modifications of the KLVFF hydrophobic core of Aβ by replacing N- and C-terminal groups with various polar moieties. Several of these terminal modifications were found to disrupt the formation of amyloid fibrils and in some cases induced the disassembly of preformed fibrils. Significantly, mitigators tha

SUBMITTER: Bett CK 

PROVIDER: S-EPMC3368634 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature