β-Structure in Human Amylin and 2 Designer β-Peptides: CD and NMR Spectroscopic Comparisons Suggest Soluble β-Oligomers and the Absence of Significant Populations of β-Strand Dimers

Intensity variation for the positive far UV CD band was observed for three ′β-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 274nm disappears completely with agitation, linking the enhancement of the 192-nm band to the highly ordered stacking of β-sheets. NMR studies indicate that the β-states of the three peptides are oligomeric, not β dimers. A membrane-forming EAK peptide displays NMR peaks due to the low concentration of ′random coil′ monomers present in slow equilibrium with β-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 β-oligomer formation.