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

Johnson, Erik C.  B.; Lanning, Jennifer D.; Meredith, Stephen C.

doi:10.1002/psc.2879

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

Journal Article · Tue Apr 26 00:00:00 EDT 2016 · Journal of Peptide Science

DOI:https://doi.org/10.1002/psc.2879· OSTI ID:1467394

Johnson, Erik C. B. ^[1]; Lanning, Jennifer D. ^[2]; Meredith, Stephen C. ^[3]

Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology, and Inst. for Biophysical Dynamics; , Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158
Univ. of Chicago, IL (United States). Dept. of Pathology
Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology; Univ. of Chicago, IL (United States). Dept. of Pathology

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.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Chicago, IL (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: FG02-04ER63786

OSTI ID:: 1467394

Journal Information:: Journal of Peptide Science, Journal Name: Journal of Peptide Science Journal Issue: 5 Vol. 22; ISSN 1075-2617

Publisher:: Wiley - European Peptide SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Alzheimer’s disease
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oligomers
peptide backbone

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

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References (24)

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