Sulfobutylether-β-Cyclodextrin for Inhibition and Rupture of Amyloid Fibrils

Anomalous aggregation of proteins into amyloid fibrils leads to various amyloidosis diseases including neurodegenerative disorders. Inhibition of fibrillation process and rupture of mature amyloid fibril/plaques using small organic molecules are the promising remedial strategies to combat neurodegenerative diseases. In this study, we present sulfobutylether-β-cyclodextrin (SBE₇β-CD), a water-soluble macrocycle, as an efficient additive to inhibit the fibril formation and also for the breakage of mature fibrils into nontoxic small particles. The steady-state and time-resolved fluorescence, circular dichroism measurements and fluorescence microscopic images collectively confirm the inhibition and rupture of the amyloid fibrils in the presence of SBE₇β-CD. In one hand, the macrocyclic encapsulation of certain amino acid residues on the protein stabilizes the native form of insulin and lysozyme and prevents their transformation into the β-sheet conformers, resulting in the inhibition of fibrillation. On the other hand, the degeneration of the fibril strands became feasible due to the overall positive charge of the fibril surface and the negative portals of the SBE₇β-CD host. Positively, the nontoxic SBE₇β-CD additive mitigates the toxicity of the system and is highly promising as therapeutics for amyloidosis

DNA-Induced Novel Optical Features of Ethyl Viologen-Tethered Perylenediimide Triad

Perylenediimide (PDI) chromophores with redox-active groups have facilitated the construction of several novel functional materials. For the first time, unusual spectroscopic changes and differential binding behavior of a tetracationic ethyl viologen tethered PDI derivative, PDEV, with calf-thymus DNA (ct-DNA) is reported here and is ascertained as due to the DNA compaction. From an initial aggregation on the DNA backbone, resulting in quenching in the emission intensity (turn off), with increase in ct-DNA concentration, a novel and strong fluorescence band (turn on) emerged in the blue region. Distinct absorption spectral changes having sharp features in vibronic patterns, increased fluorescence lifetime (from 0.33 to 4.5 ns), anisotropy values are also displayed on titration with ct-DNA corroborating the changes in microenvironment of PDEV in commensurate with structural transition from coil state to compact state. The structural changes in the DNA are also established from the circular dichroism spectra, viscosity measurements, and DNA melting data. The compaction is also directly visualized in the atomic force microscopy, scanning electron microscopy, and fluorescence microscopy images. Such compact DNA morphologies with redox-responsive donor–acceptor moieties are potential to create desired nanostructures with stimuli-responsive functionalities such as on–off switch, biosensor, drug delivery, and other optoelectronic devices