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.
Department of Chemistry, University of Washington, Seattle, WA, USA.
Kalkena
K
Sivanesam
Department of Chemistry, University of Washington, Seattle, WA, USA.
Irene
I
Shu
Department of Chemistry, University of Washington, Seattle, WA, USA.
Kelly N L
KN
Huggins
Department of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Germany.
Marianna
M
Tatarek-Nossol
Division of Peptide Biochemistry, Technische Universität München, Freising, Germany.
Aphrodite
A
Kapurniotu
Department of Chemistry, University of Washington, Seattle, WA, USA.
Niels H
NH
Andersen
D052160:Benzothiazoles; D002942:Circular Dichroism; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000235:genetics; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D010455:Peptides / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D066263:Protein Aggregation, Pathological / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation / Q000187:drug effects; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism
D052160:Benzothiazoles; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010455:Peptides; D013844:Thiazoles; C009462:thioflavin T
amyloid fibril formation; circular dichroism; cyclic β-hairpins; cytotoxicity inhibition; human pancreatic amylin; thioflavin T fluorescence; type II diabetes