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.
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.
Formaggio
Fernando
F
Institute of Biomolecular Chemistry, CNR, Department of Organic Chemistry, University of Padova, 35131 Padova, Italy. fernando.formaggio@unipd.it
Bettio
Andrea
A
Moretto
Vittorio
V
Crisma
Marco
M
Toniolo
Claudio
C
Broxterman
Quirinus B
QB
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
D000621:Aminoisobutyric Acids; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C100049:2-aminoisobutyric acid