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Title: Peptide backbone modification in the bend region of amyloid-β inhibits fibrillogenesis but not oligomer formation

Abstract

Current evidence suggests that oligomers of the amyloid-β (Aβ) peptide are involved in the cellular toxicity of Alzheimer’s disease, yet their biophysical characterization remains difficult because of lack of experimental control over the aggregation process under relevant physiologic conditions. Here in this paper, we show that modification of the Aβ peptide backbone at Gly29 allows for the formation of oligomers but inhibits fibril formation at physiologic temperature and pH. Our results suggest that the putative bend region in Aβ is important for higher-order aggregate formation.

Authors:
 [1];  [2];  [3]
+ Show Author Affiliations
  1. Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology, and Inst. for Biophysical Dynamics
  2. Univ. of Chicago, IL (United States). Dept. of Pathology
  3. Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology; Univ. of Chicago, IL (United States). Dept. of Pathology
Publication Date:
Research Org.:
Univ. of Chicago, IL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1467394
Grant/Contract Number:  
FG02-04ER63786
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Peptide Science
Additional Journal Information:
Journal Volume: 22; Journal Issue: 5; Journal ID: ISSN 1075-2617
Publisher:
Wiley - European Peptide Society
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Alzheimer’s disease; amyloidβ; oligomers; amyloid fibrils; 2-nitrobenzyl; peptide backbone

Citation Formats

Johnson, Erik C. B., Lanning, Jennifer D., and Meredith, Stephen C. Peptide backbone modification in the bend region of amyloid-β inhibits fibrillogenesis but not oligomer formation. United States: N. p., 2016. Web. doi:10.1002/psc.2879.
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Johnson, Erik C. B., Lanning, Jennifer D., & Meredith, Stephen C. Peptide backbone modification in the bend region of amyloid-β inhibits fibrillogenesis but not oligomer formation. United States. https://doi.org/10.1002/psc.2879
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Johnson, Erik C. B., Lanning, Jennifer D., and Meredith, Stephen C. Tue . "Peptide backbone modification in the bend region of amyloid-β inhibits fibrillogenesis but not oligomer formation". United States. https://doi.org/10.1002/psc.2879. https://www.osti.gov/servlets/purl/1467394.
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@article{osti_1467394,
title = {Peptide backbone modification in the bend region of amyloid-β inhibits fibrillogenesis but not oligomer formation},
author = {Johnson, Erik C. B. and Lanning, Jennifer D. and Meredith, Stephen C.},
abstractNote = {Current evidence suggests that oligomers of the amyloid-β (Aβ) peptide are involved in the cellular toxicity of Alzheimer’s disease, yet their biophysical characterization remains difficult because of lack of experimental control over the aggregation process under relevant physiologic conditions. Here in this paper, we show that modification of the Aβ peptide backbone at Gly29 allows for the formation of oligomers but inhibits fibril formation at physiologic temperature and pH. Our results suggest that the putative bend region in Aβ is important for higher-order aggregate formation.},
doi = {10.1002/psc.2879},
journal = {Journal of Peptide Science},
number = 5,
volume = 22,
place = {United States},
year = {Tue Apr 26 00:00:00 EDT 2016},
month = {Tue Apr 26 00:00:00 EDT 2016}
}
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https://doi.org/10.1002/psc.2879
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    Works referencing / citing this record:

    Factors affecting the physical stability (aggregation) of peptide therapeutics
    journal, October 2017

    • Zapadka, Karolina L.; Becher, Frederik J.; Gomes dos Santos, A. L.
    • Interface Focus, Vol. 7, Issue 6
    • DOI: 10.1098/rsfs.2017.0030
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