Isotope-assisted vibrational circular dichroism (VCD) investigations have been used to probe the site specific local structure of an amyloid peptide for the first time. A seven residue peptide, NH(2)-KLVFFAE-COOH, which represents the A beta(16-22) fragment of the Alzheimer's amyloid 13 peptide, was used for these investigations. (13)C labels were introduced separately at the carbonyl group of leucine (residue 17), alanine (residue 21) and also at both sites together. Since VCD spectra provide structure dependent signs, band shapes and frequencies, the isotope-assisted VCD spectroscopy revealed information on site specific secondary structure of the polypeptide. Isotope dilution VCD experiments provided a means to distinguish between parallel and anti-parallel nature of the beta-sheet structure formed by the A beta(16-22) fragment. The current results establish the usefulness of isotope-assisted VCD analysis in determining the site specific secondary structure of amyloid peptides. (C) 2011 Elsevier Inc. All rights reserved.