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  Solid-phase synthesis and characterization of N-terminally elongated A beta(-3-x)-peptides.

Beyer, I., Rezaei-Ghaleh, N., Klafki, H. W., Jahn, O., Haussmann, U., Wiltfang, J., et al. (2016). Solid-phase synthesis and characterization of N-terminally elongated A beta(-3-x)-peptides. Chemistry-A European Journal, 22(25), 8685-8693. doi:10.1002/chem.201600892.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-300D-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-3012-A
Genre: Journal Article

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 Creators:
Beyer, I., Author
Rezaei-Ghaleh, N.1, Author              
Klafki, H. W., Author
Jahn, O., Author
Haussmann, U., Author
Wiltfang, J., Author
Zweckstetter, M.1, Author              
Knölker, H. J., Author
Affiliations:
1Research Group of Protein Strcture Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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Free keywords: aggregation; Alzheimer's disease; biomarkers; biophysical characterization; solid-phase peptide synthesis
 Abstract: In addition to the prototypic amyloid-beta (A beta) peptides A beta(1-40) and A beta(1-42), several A beta variants differing in their amino and carboxy termini have been described. Synthetic availability of an A beta variant is often the key to study its role under physiological or pathological conditions. Herein, we report a protocol for the efficient solid-phase peptide synthesis of the N-terminally elongated Ab-peptides A beta(-3-38), A beta(-3-40), and A beta(-3-42). Biophysical characterization by NMR spectroscopy, CD spectroscopy, an aggregation assay, and electron microscopy revealed that all three peptides were prone to aggregation into amyloid fibrils. Immunoprecipitation, followed by mass spectrometry, indicated that A beta(-3-38) and A beta(-3-40) are generated by transfected cells even in the presence of a tripartite beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor. The elongated Ab peptides starting at Val(-3) can be separated from N-terminally-truncated A beta forms by high-resolution isoelectric-focusing techniques, despite virtually identical isoelectric points. The synthetic A beta variants and the methods presented here are providing tools to advance our understanding of the potential roles of N-terminally elongated A beta variants in Alzheimer's disease.

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Language(s): eng - English
 Dates: 2016-05-112016-06-13
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1002/chem.201600892
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Title: Chemistry-A European Journal
Source Genre: Journal
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Pages: - Volume / Issue: 22 (25) Sequence Number: - Start / End Page: 8685 - 8693 Identifier: -