Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly: Implications for amyloid fibril formation and materials science

• Published in: Journal of the American Chemical Society (ISSN: 0002-7863), vol. 122, num. 22, p. 5262-5277
• American Chemical Society, 2000

Deciphering the mechanism(s) of beta-sheet mediated self-assembly is essential for understanding amyloid fibril formation and for the fabrication of polypeptide materials. Herein, we report a simple peptidomimetic that self-assembles into polymorphic beta-sheet quaternary structures including protofilaments, filaments, fibrils, and ribbons that are reminiscent of the highly ordered structures displayed by the amyloidogenic peptides A beta, calcitonin, and amylin. The distribution of quaternary structures can be controlled by and in some cases specified by manipulating the pH, buffer composition, and the ionic strength. The ability to control beta-sheet-mediated assembly takes advantage of quaternary structure dependent pK(a) perturbations. Biophysical methods including analytical ultracentrifugation studies as well as far-UV circular dichroism and FT-IR spectroscopy demonstrate that linked secondary and quaternary structural changes mediate peptidomimetic self-assembly. Electron and atomic force microscopy reveal that peptidomimetic assembly involves numerous quaternary structural intermediates that appear to self-assemble in a convergent fashion affording quaternary structures of increasing complexity. The ability to control the assembly pathway(s) and the final quaternary structure(s) afforded should prove to be particularly useful in deciphering the quaternary structural requirements for amyloid fibril formation and for the construction of noncovalent macromolecular structures

Keywords: x-ray-diffraction ; protected peptide-fragments ; circular-dichroism spectra ; antiparallel beta-sheet ; atomic-force microscopy ; solid-phase synthesis ; polymer-bound oxime ; c-terminal peptide ; alzheimers-disease ; in-vitro

Reference

• LMNN-ARTICLE-2009-009
• doi:10.1021/ja9937831

Record created on 2009-10-29, modified on 2017-05-12