Cavini, Italo A. and Munte, Claudia E. and Erlach, Markus Beck and van Groen, Thomas and Kadish, Inga and Zhang, Tao and Ziehm, Tamar and Nagel-Steger, Luitgard and Kutzsche, Janine and Kremer, Werner and Willbold, Dieter and Kalbitzer, Hans Robert (2018) Inhibition of amyloid Ab aggregation by high pressures or specific D-enantiomeric peptides. CHEMICAL COMMUNICATIONS, 54 (26). pp. 3294-3297. ISSN 1359-7345, 1364-548X
Full text not available from this repository. (Request a copy)Abstract
Pressure can shift the polymer-monomer equilibrium of A beta, increasing pressure first leads to a release of A beta-monomers, surprisingly at pressures higher than 180 MPa repolymerization is induced. By high pressure NMR spectroscopy, differences of partial molar volumes Delta V-0 and compressibility factors Delta beta' of polymerization were determined at different temperatures. The D-enantiomeric peptides RD2 and RD2D3 bind to monomeric A beta with affinities substantially higher than those determined for fibril formation. By reducing the A beta concentration below the critical concentration for polymerization they inhibit the formation of toxic oligomers. Chemical shift perturbation allows the identification of the binding sites. The D-peptides are candidates for drugs preventing Alzheimer's disease. We show that RD2D3 has a positive effect on the cognitive behaviour of transgenic (APPSwDI) mice prone to Alzheimer's disease. The heterodimer complexes have a smaller Stokes radius than A beta alone indicating the recognition of a more compact conformation of A beta identified by high pressure NMR before.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ALZHEIMERS-DISEASE; TRANSGENIC MICE; BETA-PEPTIDE; SOLUTION NMR; AMYLOID-BETA(1-42); PROTOFIBRILS; IMPROVES; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Mar 2020 13:36 |
| Last Modified: | 10 Mar 2020 13:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14747 |
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