CONFORMATIONAL-ANALYSIS OF THE BETA-AMYLOID PEPTIDE FRAGMENT, BETA(12-28)

NMR and CD spectroscopy have been used to examine the conformation of the peptide, beta(12-28), (VHHQKLVFFAEDVGSNK) in aqueous and 60% TFE/4 0% H2O solution at pH 2.4. In 60% TFE solution, the peptide is helical as confirmed by the CD spectrum and by the pattern of the NOE cross p eaks detected in the NOESY spectrum of the peptide. In aqueous solutio n, the peptide adopts a more extended and flexible conformation. Broad ening of resonances at low temperature, temperature-dependent changes in the chemical shifts of several of the CHalpha resonances and the ob servation of a number of NOE contacts between the hydrophobic side-cha in protons of the peptide are indicative of aggregation in aqueous sol ution. The behavior of beta(12-28) in 60% TFE and in aqueous solution are consistent with the overall conformation and aggregation behavior reported for the larger peptide fragment beta(1-28) and the parent bet a-amyloid peptide.