Tarabara U. Spectroscopic and molecular dynamic study of fibrillar aggregates of proteins

The dissertation addresses an important problem of modern physics of biopolymers concerning the elucidation of molecular mechanisms behind the protein structural transition from native conformation into aggregated fibrillar state. The goal of the study was to characterize the interaction of the novel fluorochromes with fibrillar protein aggregates and to uncover the molecular determinants of fibrillization process. From the practical viewpoint, the examined hepta- and trimethine cyanine dyes can be used in the development of multichromophoric and multiparametric assays for differentiation between the native and fibrillar states of protein molecules. The proposed approach to identification of amyloid fibrils through measuring the efficiency of cascade energy transfer between the amyloid-specific chromophores is important for elaboration of highly sensitive methods of medical diagnostics in vivo, the high accuracy and informativeness of which will arise from the combination of advantages of individual fluorochromes, such as, in particular, high quantum yield of the main donor and significant effective Stokes shift, allowing to perform diagnostics in the region of low autofluorescence of biological tissues. The results obtained open the avenue for the applications of cFRET in the structural analysis of fibrillar protein aggregates. The models and methodological approaches developed in this study can be used in probing the amyloid specificity and sensitivity of newly synthesized dyes