Probing the amyloid protein aggregates with unsymmetrical monocationic trimethine cyanine dyes

A series of novel trimethine cyanine dyes were synthesized and evaluated as potential probes for the detection of pathogenic protein aggregates, amyloid fibrils. The spectral properties of the chromophores were scrutinized in a free state as well as in the presence of non-fibrillized and fibrillar insulin emphasizing the cyanine aggregation that accompany the dye-protein interactions. The trimethines under study were found to be non-fluorescent in aqueous media and when bound to the non-fibrillized protein due to the H-aggregation of trimethines being more pronounced in the case of the control insulin. Depending on the variations with respect to the N-alkyl fragment of the benzothiazolic moiety, the dyes are increasing their emission signal in dozens of times in the presence of fibrillar insulin. The fluorescence turn-on responses observed upon binding of the AK3-11 cyanine dye to the insulin amyloid fibrils are attributed to a self-staking to non-staking transition of this trimethine. Overall, we demonstrated that trimethine cyanine dyes are prospective amyloid probes capable amyloid probes capable of operating in both fluorescence and absorption modes. (C) 2020 Published by Elsevier B.V.