期刊
PEPTIDES
卷 31, 期 2, 页码 248-256出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2009.12.001
关键词
beta-Amyloid; Oligomers; Aggregation; Alzheimer's disease; Isopeptide
资金
- Hungarian National Sciences Foundation [OTKA NK 73672]
- NKTH
- Janos Bolyai Postdoctoral Fellowship
- [FP-7 201159]
- [FP-7 211696]
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.
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