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

Versions of a previously discovered β‐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. A strategy that stabilizes the hairpin conformation increases inhibitor potency. Substoichiometric amounts of a cyclic β‐hairpin peptide are able to inhibit IAPP amyloidogenesis. Verification that hairpin‐like conformation is involved in the inhibition of IAPP cytotoxicity.