BETA-STRUCTURE IN HUMAN AMYLIN AND 2 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 t hree 'beta-sheet' peptides. In 6% HFIP, an amyloidogenic species (huma n pancreatic amylin) displays, on standing, an extremely intense 192-n m band which diminishes upon physical agitation. A concurrently formed Tyr sidechain band at 274nm disappears completely with agitation, lin king the enhancement of the 192-nm band to the highly ordered stacking of beta-sheets. NMR studies indicate that the beta-states of the thre e peptides are oligomeric, not beta dimers. A membrane-forming EAK pep tide 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 ban d, contain only oligomeric species. NMR studies at 25% HFIP revealed t he structural requirements for inhibition of beta-oligomer formation. (C) 1994 Academic Press, Inc.