Controlled in situ preparation of A beta(1-42) oligomers from the isopeptide "iso-A beta(1-42)", physicochemical and biological characterization

beta-Amyloid (A beta) peptides play a crucial role in the pathology of the neurodegeneration in Alzheimer's disease (AD). Biological experiments (both in vitro and animal model studies of AD) require synthetic A beta peptides of standard quality, aggregation grade, neurotoxicity and water solub...

Full description

Saved in:
Bibliographic Details
Main Authors: Bozsó Zsolt
Penke Botond
Simon Dóra
Laczkó Ilona
Juhász Gábor
Szegedi Viktor
Kasza Ágnes
Soós Katalin
Hetényi Anasztázia
Wéber Edit
Tóháti Hajnalka-Mária
Czirjákné Csete Mária
Zarándi Márta
Fülöp Lívia
Format: Article
Published: 2010
Series:PEPTIDES 31 No. 2
doi:10.1016/j.peptides.2009.12.001

mtmt:1329681
Online Access:http://publicatio.bibl.u-szeged.hu/10392
Description
Summary:beta-Amyloid (A beta) peptides play a crucial role in the pathology of the neurodegeneration in Alzheimer's disease (AD). Biological experiments (both in vitro and animal model studies of AD) require synthetic A beta peptides of standard quality, aggregation grade, neurotoxicity and water solubility. The synthesis of A beta peptides has been difficult, owing to their hydrophobic character, poor solubility and high tendency for aggregation. Recently an isopeptide precursor (iso-A beta(1-42)) was synthesized by Fmoc-chemistry and transformed at neutral pH to A beta(1-42) by O -> N acyl migration in a short period of time. We prepared the same precursor peptide using Boc-chemistry and studied the transformation to A beta(1-42) by acyl migration. The peptide conformation and aggregation processes were studied by several methods (circular dichroism, atomic force and transmission electron microscopy, dynamic light scattering). The biological activity of the synthetic A beta(1-42) was measured by ex vivo (long-term potentiation studies in rat hippocampal slices) and in vivo experiments (spatial learning of rats). It was proven that O -> N acyl migration of the precursor isopeptide results in a water soluble oligomeric mixture of neurotoxic A beta(1-42). These oligomers; are formed in situ just before the biological experiments and their aggregation grade could be standardized. (C) 2009 Elsevier Inc. All rights reserved.
Physical Description:248-256
ISSN:0196-9781