Influence of phosphorus dendrimers on the aggregation of the prion peptide PrP 185-208.
Inhibition of fibril assembly is a potential therapeutic strategy in prion diseases. The effect of cationic phosphorous dendrimers on the aggregation process of the prion peptide PrP 185-208 was studied using a spectrofluorometric assay with thioflavin T (ThT) and Fourier transformed infrared spectroscopy in order to monitor the kinetics of the process and the changes in the peptide secondary structure. The results show that phosphorous dendrimers are able to clearly interfere with PrP 185-208 aggregation process by both slowing down the formation of aggregates (by causing a decrease of the nucleation rate) and by lowering the final amount of amyloid fibrils, a common hallmark of conformational diseases. The dendrimers effect on the aggregation process would imply their interaction with peptide monomers and oligomers during the nucleation phase.
Klajnert
Barbara
B
Department of General Biophysics, University of Lodz, 12/16 Banacha Street, 90-237 Lodz, Poland. aklajn@biol.uni.lodz.pl
Cortijo-Arellano
Marta
M
Cladera
Josep
J
Majoral
Jean-Pierre
JP
Caminade
Anne-Marie
AM
Bryszewska
Maria
M
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D052160:Benzothiazoles; D050091:Dendrimers / Q000494:pharmacology*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D010758:Phosphorus / Q000494:pharmacology*; D018621:PrPC Proteins / Q000737:chemistry* / Q000648:ultrastructure; D011328:Prions / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013844:Thiazoles
D000682:Amyloid; D052160:Benzothiazoles; D050091:Dendrimers; D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions; D013844:Thiazoles; C524422:prion protein (185-208); C009462:thioflavin T; D010758:Phosphorus