Back
Chiral recognition in amyloid fiber growth.
Journal article

Chiral recognition in amyloid fiber growth.

  • Torbeev V Institut de Science et d'Ingénierie Supramoléculaires, International Center for Frontier Research in Chemistry, UMR 7006, Université de Strasbourg, 8 allée Gaspard Monge, 67000, Strasbourg, France.
  • Grogg M Laboratory of Organic Chemistry, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, Zürich, CH-8093, Switzerland.
  • Ruiz J Institut de Science et d'Ingénierie Supramoléculaires, International Center for Frontier Research in Chemistry, UMR 7006, Université de Strasbourg, 8 allée Gaspard Monge, 67000, Strasbourg, France.
  • Boehringer R Institut de Science et d'Ingénierie Supramoléculaires, International Center for Frontier Research in Chemistry, UMR 7006, Université de Strasbourg, 8 allée Gaspard Monge, 67000, Strasbourg, France.
  • Schirer A Laboratoire de Bioélectrochimie et Spectroscopie, Chimie de la Matière Complexe, UMR 7140, Université de Strasbourg-CNRS, 1 rue Blaise Pascal, 67070, Strasbourg, France.
  • Hellwig P Laboratoire de Bioélectrochimie et Spectroscopie, Chimie de la Matière Complexe, UMR 7140, Université de Strasbourg-CNRS, 1 rue Blaise Pascal, 67070, Strasbourg, France.
  • Jeschke G Laboratory of Physical Chemistry, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, Zürich, CH-8093, Switzerland.
  • Hilvert D Laboratory of Organic Chemistry, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, Zürich, CH-8093, Switzerland.
Show more…
  • 2016-03-02
Published in:
  • Journal of peptide science : an official publication of the European Peptide Society. - 2016
chemical protein synthesis
mirror-image proteins
protein misfolding and aggregation
β2-microglobulin
Amyloid
Humans
Models, Molecular
Peptides
Protein Structure, Secondary
Spectroscopy, Fourier Transform Infrared
Stereoisomerism
beta 2-Microglobulin
English Insoluble amyloid fibers represent a pathological signature of many human diseases. To treat such diseases, inhibition of amyloid formation has been proposed as a possible therapeutic strategy. d-Peptides, which possess high proteolytic stability and lessened immunogenicity, are attractive candidates in this context. However, a molecular understanding of chiral recognition phenomena for d-peptides and l-amyloids is currently incomplete. Here we report experiments on amyloid growth of individual enantiomers and their mixtures for two distinct polypeptide systems of different length and structural organization: a 44-residue covalently-linked dimer derived from a peptide corresponding to the [20-41]-fragment of human β2-microglobulin (β2m) and the 99-residue full-length protein. For the dimeric [20-41]β2m construct, a combination of electron paramagnetic resonance of nitroxide-labeled constructs and (13) C-isotope edited FT-IR spectroscopy of (13) C-labeled preparations was used to show that racemic mixtures precipitate as intact homochiral fibers, i.e. undergo spontaneous Pasteur-like resolution into a mixture of left- and right-handed amyloids. In the case of full-length β2m, the presence of the mirror-image d-protein affords morphologically distinct amyloids that are composed largely of enantiopure domains. Removal of the l-component from hybrid amyloids by proteolytic digestion results in their rapid transformation into characteristic long straight d-β2m amyloids. Furthermore, the full-length d-enantiomer of β2m was found to be an efficient inhibitor of l-β2m amyloid growth. This observation highlights the potential of longer d-polypeptides for future development into inhibitors of amyloid propagation. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/112898
Statistics
Document views: 26 File downloads: