Inhibition of amyloid Aß aggregation by high pressures or specific D-enantiomeric peptides.
CAVINI, Italo A.; MUNTE, Claudia Elisabeth; ERLACH, Markus Beck; GROEN, Thomas van; KADISH, Inga; ZHANG, Tao; ZIEHM, Tamar; NAGEL-STEGER, Luitgard; KUTZSCHE, Janine; KREMER, Werner; WILLBOLD, Dieter; KALBITZER, Hans Robert.
CAVINI, Italo A.; MUNTE, Claudia Elisabeth; ERLACH, Markus Beck; GROEN, Thomas van; KADISH, Inga; ZHANG, Tao; ZIEHM, Tamar; NAGEL-STEGER, Luitgard; KUTZSCHE, Janine; KREMER, Werner; WILLBOLD, Dieter; KALBITZER, Hans Robert.
 Abstract: Pressure can shift the polymer-monomer equilibrium of Aß, increasing pressure first leads to a release of Aß-monomers, surprisingly at pressures higher than 180 MPa repolymerization is induced. By high pressure NMR spectroscopy, differences of partial molar volumes ?V and compressibility factors ?ß' of polymerization were determined at different temperatures. The D-enantiomeric peptides RD2 and RD2D3 bind to monomeric Aß with affinities substantially higher than those determined for fibril formation. By reducing the Aß 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 Aß alone indicating the recognition of a more compact conformation of Aß identified by high pressure NMR before. | |
| Chemical Communications |
| v. 54, n. 26, p. 3294-3297 - Ano: 2018 |
| Fator de Impacto: 6,319 |
| http://dx.doi.org/10.1039/C8CC01458B |  @article={002878592,author = {CAVINI, Italo A.; MUNTE, Claudia Elisabeth; ERLACH, Markus Beck; GROEN, Thomas van; KADISH, Inga; ZHANG, Tao; ZIEHM, Tamar; NAGEL-STEGER, Luitgard; KUTZSCHE, Janine; KREMER, Werner; WILLBOLD, Dieter; KALBITZER, Hans Robert.},title={Inhibition of amyloid Aß aggregation by high pressures or specific D-enantiomeric peptides},journal={Chemical Communications},note={v. 54, n. 26, p. 3294-3297},year={2018}} |
