4.5 Article

Peptide Inhibitors of the amyloidogenesis of IAPP: verification of the hairpin-binding geometry hypothesis

Journal

FEBS LETTERS
Volume 590, Issue 16, Pages 2575-2583

Publisher

WILEY-BLACKWELL
DOI: 10.1002/1873-3468.12261

Keywords

amyloid fibril formation; circular dichroism; cyclic beta-hairpins; cytotoxicity inhibition; human pancreatic amylin; thioflavin T fluorescence; type II diabetes

Funding

  1. National Institutes of Health (NIH) [GM099889]
  2. Deutsche Forschungsgemeinschaft

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Versions of a previously discovered -hairpin peptide inhibitor of IAPP aggregation that are stabilized in that conformation, or even forced to remain in the hairpin conformation by a backbone cyclization constraint, display superior activity as inhibitors. The cyclized hairpin, cyclo-WW2, displays inhibitory activity at substoichiometric concentrations relative to this amyloidogenic peptide. The hairpin-binding hypothesis stands confirmed.

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