title: Disruption of the beta-sheet structure of a protected pentapeptide, related to the beta-amyloid sequence 17-21, induced by a single, helicogenic C(alpha)-tetrasubstituted alpha-amino acid.
abstract: Fifteen years ago it was shown that an alpha-aminoisobutyric acid (Aib) residue is significantly more effective than an L-Pro or a D-amino acid residue in inducing beta-sheet disruption in short model peptides. As this secondary structure element is known to play a crucial role in the neuropathology of Alzheimer's disease, it was decided to check the effect of Aib (and other selected, helix inducer, C(alpha)-tetrasubstituted alpha-amino acids) on the beta-sheet conformation adopted by a protected pentapeptide related to the sequence 17-21 of the beta-amyloid peptide. By use of FT-IR absorption and 1H NMR techniques it was found that the strong self-association characterizing the pentapeptide molecules in weakly polar organic solvents is completely abolished by replacing a single residue with Aib or one of its congeners.
authors.affiliation: Institute of Biomolecular Chemistry, CNR, Department of Organic Chemistry, University of Padova, 35131 Padova, Italy. fernando.formaggio@unipd.it
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.forename: Andrea
authors.initials: A
authors.lastname: Bettio
authors.forename: Vittorio
authors.initials: V
authors.lastname: Moretto
authors.forename: Marco
authors.initials: M
authors.lastname: Crisma
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
authors.forename: Quirinus B
authors.initials: QB
authors.lastname: Broxterman
mesh_terms: D019943:Amino Acid Substitution; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000621:Aminoisobutyric Acids; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C100049:2-aminoisobutyric acid