NR AXPZ
AU Klajnert,B.; Cladera,J.; Bryszewska,M.
TI Can Dendrimers Block the Formation of Fibrils?
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.41
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Dendrimers are a new class of polymers with a well-defined molecular structure. They adopt a spherical shape and are prepared in a step-wise manner from branched monomer units. The more layers that are attached, the higher the so-called generation of dendrimer is. Dendrimers are promising materials in many biomedical applications such as transfection of DNA and carrying drugs. Recently, it has been shown that dendrimers have their own potentially therapeutic activity against prion diseases [1]. The potency of amino-terminated dendrimers in eliminating PrPsc from ScN2a cells was proved. It was suggested that the presence of amino surface groups that increases with generation was crucial for purging activity. These promising results encouraged studies on other types of dendrimers. Solassol et al. successfully tested phosphorus containing cationic dendrimers for anti-prion activity [2].
Objectives: We used an alternative method to cell-based assays to screen the antiprion dendrimers. Truncated prion peptides in the absence of cellular factors were exposed to destabilizing factors to mimic the conditions that lead to creation of fibrils.
Methods: The accumulation of amyloids was monitored by changes in the fluorescence of thioflavine T, which is sensitive to the presence of amyloid fibrils. These studies were accompanied by Fourier transformed infrared spectroscopy to check the impact of dendrimers on the secondary structure of peptides and by electron microscopy to observe morphology of fibrils.
Results: It has been shown that the higher the dendrimer generation, the larger the degree of inhibition of the amyloid aggregation process and the more effective dendrimers are in disrupting the already existing fibrils.
Discussion: The mechanisms of inhibiting amyloidogenesis by dendrimers were formed [3, 4]. It has been postulated that dendrimers can interact with peptide monomers, block fibril ends and break existing fibrils.
1. Supattapone, S. Nguyen, H.-O. B., Cohen, F. E., Prusiner, S. B. & Scott, M. R. (1999) Proc. Natl. Ac. Sci. 96, 14529
2. Solassol, J., Crozet, C., Perrier, V., Leclaire, J., Béranger, F., Caminade, A.-M., Meunier, B., Dormont, D., Majoral, J.-P. & Lehmann, S. (2004) J. Gen. Virol. 85, 1791
3. Klajnert, B., Cortijo-Arellano, M., Cladera, J. & Bryszewska, M. (2006) Biochem. Biophys. Res. Commun. 345, 21
4. Klajnert, B., Cladera, J. & Bryszewska, M. (2006) Biomacromol. 7, 2186
AD B.Klajnert, M. Bryszewska, University of Lodz, Department of General Biophysics, Poland; J. Cladera, Universitat Autonoma de Barcelona, Department of Biochemistry and Molecular Biology, Spain
SP englisch
PO Schottland