NR ATRG
AU Hafner Bratkovic,I.; Smid,L.; Rupnik,M.; Petric,A.; Bresjanac,M.; Jerala,R.
TI Binding specificity of dyes to prion amyloids in vitro and to prion plaques
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-22
PT Konferenz-Poster
AB
Over the past decade several tracers have been tested for the use in in vivo diagnostics of amyloidoses by functional neuroimaging techniques such as positron emission tomography (PET) and single photon emission computed tomography. Most of the work has been aimed at detecting beta-amyloid plaques and neurofibrillary tangles, markers of Alzheimer disease. Agents suitable for in vivo detection of amyloid brain deposits must meet several criteria, but most important they have to bind to amyloid with high specificity and have to be able to cross the blood-brain barrier. Main types of PET-tracers currently under development are derived from thioflavin T, Congo Red (styrylbenzene) and aminonaphthalene backbones.
We have characterized binding of compounds belonging to different above mentioned chemotypes (thioflavin T, BTA-1, congo red, FDDNP etc.) and several other species (curcumin, acridin orange) to recombinant prion protein in amyloid and alpha form using direct and competitive fluorimetric binding assays. Binding specificity has been further evaluated by confocal microscopy on sections from human patients and their spectral characteristics compared with in vitro results. Presence of distinct classes of binding sites on amyloid form of prion protein was observed. Binding of different dyes will contribute to the understanding of prion aggregate structures and may represent the lead for potential inhibitors of prion replication.
AD Iva Hafner Bratkovic, Roman Jerala, National institute of Chemistry, Slovenia; Lojze Smid, Maja Bresjanac, University of Ljubljana, Medical faculty, Slovenia; Andrej Petric, University of Ljubljana, Faculty of chemistry and chemical technology, Slovenia; Marjan Rupnik, European Neuroscience Institute, Germany
SP englisch
PO Deutschland