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. |
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Authors: | Fernando Formaggio Andrea Bettio Vittorio Moretto Marco Crisma Claudio Toniolo Quirinus B Broxterman |
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Institution: | Institute of Biomolecular Chemistry, CNR, Department of Organic Chemistry, University of Padova, 35131 Padova, Italy. fernando.formaggio@unipd.it |
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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. |
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Keywords: | amyloid‐related sequence helix inducer infrared absorption nuclear magnetic resonance β‐sheet breaker β‐sheet structure Cα‐tetrasubstituted α‐amino acid |
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