Beta-structure in human amylin and two designer beta-peptides: CD and NMR spectroscopic comparisons suggest soluble beta-oligomers and the absence of significant populations of beta-strand dimers.
Intensity variation for the positive far UV CD band was observed for three 'beta-sheet' peptides. In 6% HFIP, an amyloidogenic species (human pancreatic amylin) displays, on standing, an extremely intense 192-nm band which diminishes upon physical agitation. A concurrently formed Tyr sidechain band at 274 nm disappears completely with agitation, linking the enhancement of the 192-nm band to the highly ordered stacking of beta-sheets. NMR studies indicate that the beta-states of the three peptides are oligomeric, not beta dimers. A membrane-forming EAK peptide displays NMR peaks due to the low concentration of 'random coil' monomers present in slow equilibrium with beta-oligomers; solutions of a more hydrophobic ELKA peptide, which displays an intense 195-nm band, contain only oligomeric species. NMR studies at 25% HFIP revealed the structural requirements for inhibition of beta-oligomer formation.
Cort
J
J
Department of Chemistry, University of Washington, Seattle 98195.
Liu
Z
Z
Lee
G
G
Harris
S M
SM
Prickett
K S
KS
Gaeta
L S
LS
Andersen
N H
NH
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D058228:Islet Amyloid Polypeptide; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012995:Solubility
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D046911:Macromolecular Substances; D010455:Peptides