Peptide backbone modification in the bend region of amyloid-β inhibits fibrillogenesis but not oligomer formation.
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, 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. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA.|Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, 60637, USA.
Erik C B
EC
Johnson
Department of Pathology, The University of Chicago, Chicago, IL, 60637, USA.
Jennifer D
JD
Lanning
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA.|Department of Pathology, The University of Chicago, Chicago, IL, 60637, USA.
Stephen C
SC
Meredith
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics*; D005998:Glycine / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D009154:Mutation; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D013696:Temperature
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D005998:Glycine
2-nitrobenzyl; Alzheimer's disease; amyloid fibrils; amyloid-β; oligomers; peptide backbone