Aggregation on an amyloid peptide as studied by NMR diffusometry and 2D NMR noesy spectroscopy
2009 (English)In: Protein folds in infectious and neurodegenerative diseases, Centre National de la Recherche Scientifique, CNRS , 2009, 91- p.Conference paper, Meeting abstract (Other academic)
Alzheimer's disease is a progressive neurodegenerative disorder affecting millions of people world-wide. Alzheimer's amyloid-b peptide forms amorphous aggregates or amyloid fibrils. However, recent studies indicate that soluble oligomers instead of fibrils may form probably most neurotoxic species. These oligomeric aggregates are difficult to study by traditional structural experimental techniques. NMR diffusometry offer useful additional possibilities. In freshly-prepared solutions (without any pre-aggregates of the peptide) diffusion of the peptide can often be described by an unique diffusion kinetics, which corresponds to the calculated diffusion coefficient of the amyloid- b peptide monomers with the Stokes-Einstein hard-sphere approximation (typically D ~10-10 m2/s). In a quasi-equilibrium or in pulse-induced conditions, new larger aggregates of Ab with diffusion coefficients down to <1×10-13 m2/s were detected. 2D 1H NMR NOESY provides both an additional evidence of aggregation and also reveals most probable sites of the side chain interactions in the aggregates. "Pulse-like" treatment of the sample involves: (i) changing of the solution composition; (ii) freezing-thawing; and (iii) sonication of the sample in the course of its incubation. Putative aggregation mechanisms and structures of monomers and oligomers in solutions at different conditions are discussed.1. Filippov A., Sulejmanova A., Antzutkin O. and Gröbner G. (2005) Diffusion and aggregation of Alzheimer's Abeta(1-40)-peptide in aqueous-TFE solutions as studied by pulsed field gradient NMR. Applied Magnetic Resonance. 29. 439 - 449.2. Filippov A., Sulejmanova A., Gröbner G. and Antzutkin O. (2008) Effect of freezing on amyloid peptide aggregation and self-diffusion in an aqueous solution. Colloid J. 70. 501-506.3. Filippov A., Gröbner G. and Antzutkin O. Effect of ultrasonication on amyloid peptide aggregation in trifluoroethanol solution. (in preparation).
Place, publisher, year, edition, pages
Centre National de la Recherche Scientifique, CNRS , 2009. 91- p.
Research subject Chemistry of Interfaces
IdentifiersURN: urn:nbn:se:ltu:diva-38379Local ID: cc0e0630-93ad-11de-8da0-000ea68e967bOAI: oai:DiVA.org:ltu-38379DiVA: diva2:1011879
International Jacques Monod Conference : Protein folds in infectious and neurodegenerative diseases 25/04/2009 - 29/04/2009
Godkänd; 2009; 20090828 (ysko)2016-10-032016-10-032017-01-19Bibliographically approved