Search academic texts

Information × Registration Number 0218U001116, 0116U000937 , R & D reports Title Development of the novel methods of fluorescence diagnostics of amyloid pathologies popup.stage_title Head Trusova Valeriya, Доктор фізико-математичних наук Registration Date 28-02-2018 Organization Kharkov National University named after V.N. Karazin popup.description2 The goal of the study consisted in characterizing of the protein binding sites of the novel benzanthrone and squaraine fluorescence amyloid markers using a fluorescence spectroscopy. Furthermore, we aimed at uncovering the factors, that may affect photophysical properties of the fluorophores bound to the pathogenic protein aggregates, using quantum-chemical studies and correlation analysis. Finally, at the last step of the study testing of inhibitors of amyloidogenesis has been performed. The objects of the study - physical processes and mechanisms of the formation of the fluorescence response of the novel dyes in the presence of amyloid fibrils and under the influence of the modulators of the amyloidogenesis. Methods of investigation - absorption and fluorescence spectroscopy, quantum-chemical calculations, computer modeling. The results of F?rster resonance energy transfer study allowed us to suggest that benzanthrone dyes are bound to the grooves running parallel to the long axis of the ?-sheet. Quantum-chemical calculations and QSAR analysis showed a positive correlation between the sensitivity of the best benzanthrone amyloid markers to amyloid fibrils and a number of molecular descriptors. Using the ThT assay, it has been demonstrated that all types of PoxnoPC assemblies induced the retardation of the nucleation and elongation phases, while PazePC micelles completely inhibited protein aggregation at low protein-to-lipid molar ratios. Furthermore, it has been shown that trimethine cyanine dyes are the most effective inhibitors of the amyloid fibril growth. In turn, monomethine dyes and heptamethine fluorophore AK7-6 appeared to be the least effective inhibitors of this process. In conclusion, the revealed molecular mechanisms of interaction of the novel amyloid markers and inhibitors of amyloidogenesis with the fibrillar protein aggregates could be successfully employed for the development of the anti-amyloid strategies. Product Description popup.authors В. Трусова К. Вус О. Рижова У. Тарабара popup.nrat_date 2020-04-02 Close