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

Z. Bozsó, B. Penke, Dóra Simon, I. Laczkó, G. Juhász, Viktor Szegedi, Ágnes Kasza, K. Soós, A. Hetényi, Edit Wéber, Hajnalka Tóháti, M. Csete, Márta Zarándi, L. Fülöp

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

β-Amyloid (Aβ) 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 Aβ peptides of standard quality, aggregation grade, neurotoxicity and water solubility. The synthesis of Aβ peptides has been difficult, owing to their hydrophobic character, poor solubility and high tendency for aggregation. Recently an isopeptide precursor (iso-Aβ(1-42)) was synthesized by Fmoc-chemistry and transformed at neutral pH to Aβ(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 Aβ(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 Aβ(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 Aβ(1-42). These oligomers are formed in situ just before the biological experiments and their aggregation grade could be standardized.

Original languageEnglish
Pages (from-to)248-256
Number of pages9
JournalPeptides
Volume31
Issue number2
DOIs
Publication statusPublished - Feb 2010

Fingerprint

Oligomers
Agglomeration
Peptides
Solubility
Rats
Alzheimer Disease
Water
Long-Term Potentiation
Experiments
Pathology
Dynamic light scattering
Circular Dichroism
Bioactivity
Transmission Electron Microscopy
Amyloid
Conformations
Animals
Animal Models
Transmission electron microscopy

Keywords

  • β-Amyloid
  • Aggregation
  • Alzheimer's disease
  • Isopeptide
  • Oligomers

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Controlled in situ preparation of Aβ(1-42) oligomers from the isopeptide "iso-Aβ(1-42)", physicochemical and biological characterization. / Bozsó, Z.; Penke, B.; Simon, Dóra; Laczkó, I.; Juhász, G.; Szegedi, Viktor; Kasza, Ágnes; Soós, K.; Hetényi, A.; Wéber, Edit; Tóháti, Hajnalka; Csete, M.; Zarándi, Márta; Fülöp, L.

In: Peptides, Vol. 31, No. 2, 02.2010, p. 248-256.

Research output: Contribution to journalArticle

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