Journal article
Probing the Role of Backbone Hydrogen Bonding in β-Amyloid Fibrils with Inhibitor Peptides Containing Ester Bonds at Alternate Positions
Biochemistry (Easton), Vol.42(2), pp.475-485
01/21/2003
DOI: 10.1021/bi0259857
PMID: 12525175
Abstract
Protein-protein interactions are frequently mediated by stable, intermolecular β-sheets. A number of cytokines and the HIV Protease, for example, dimerize through β-sheet motifs. Evidence also suggests that the macromolecular assemblies of peptides and proteins in amyloid fibrils are stabilized by intermolecular β-sheets. In this paper, we report that interfering with the backbone hydrogen bonding of an amyloidgenic peptide (Aβ16-20) by replacing amide bonds with ester bonds prevents the aggregation of the peptide. The ester bonds were incorporated in an alternating fashion so that the peptide presents two unique hydrogen bonding faces when arrayed in an extended, β-strand conformation; one face of the peptide has normal hydrogen bonding capabilities, but the other face is missing amide protons and its ability to hydrogen bond is severely limited. Analytical ultracentrifugation experiments demonstrate that this ester peptide, Aβ16-20e, is predominantly monomeric under solution conditions, unlike the fibril-forming Aβ16-20 peptide. Aβ16-20e also inhibits the aggregation of the Aβ1-40 peptide and disassembles preformed Aβ1-40 fibrils. These results suggest that backbone hydrogen bonding is critical for the assembly of amyloid fibrils.
Details
- Title: Subtitle
- Probing the Role of Backbone Hydrogen Bonding in β-Amyloid Fibrils with Inhibitor Peptides Containing Ester Bonds at Alternate Positions
- Creators
- David J. Gordon - University of ChicagoStephen C. Meredith - University of Chicago
- Resource Type
- Journal article
- Publication Details
- Biochemistry (Easton), Vol.42(2), pp.475-485
- Publisher
- American Chemical Society
- DOI
- 10.1021/bi0259857
- PMID
- 12525175
- ISSN
- 0006-2960
- eISSN
- 1520-4995
- Language
- English
- Date published
- 01/21/2003
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984354157302771
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