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

Abstract

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 (SBE 7 β-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 SBE 7 β-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 SBE 7 β-CD host. Positively, the nontoxic SBE 7 β-CD additive mitigates the toxicity of the system and is highly promising as therapeutics for amyloidosis.

Supramolecular Nanorods of (N-Methylpyridyl) Porphyrin With Captisol: Effective Photosensitizer for Anti-bacterial and Anti-tumor Activities

“…Moreover, the cell viability data obtained with the captisol alone revealed no cytotoxicity with ~75 μM of captisol, which is used in these studies. Similar non-toxic data were observed in our earlier study using insulin fibrils (Shinde et al, 2017), where we did not observe any cytotoxicity effect of captisol up to ~250 μM using CHO cell lines. Thus, it is confirmed that complexation of TMPyP with Captisol reduced its inherent toxicity.…”

“…On its technological application, our recent work on ultra-bright rhodamines with SBE 7 βCD (captisol) in water has demonstrated the construction of a practical water-based dye laser system (Khurana et al, 2018). Further studies on its biological/medicinal application, we have established that the benign captisol macrocycle can be effectively used to inhibit and disintegrate amyloid fibrils/plaques, signifying its role as therapeutic agent toward neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases (Shinde et al, 2017). In the present study, we anticipate that the interaction of negatively charged captisol portals with the four N-methylpyridyl ends of TMPyP will prevent the inherent self-assembling behavior of TMPyP and will deaggregate the π-stacked porphyrins, which will improve its photophysical properties and enhance their active singlet oxygen yield.…”

Oligomeric procyanidins inhibit insulin fibrillation by forming unstructured and off-pathway aggregates

“…[14][15][16] Moreover, insulin brils can be formed in vitro under certain destabilizing conditions, including evaluated temperature, low pH, and increased ionic strength, which has been a formidable challenge to long-distance shipping and long-term storage of insulin. 17,18 Small-molecule inhibitors have been widely investigated to inhibit protein amyloid, such as b-cyclodextrin, 19 phenolic compounds, 20,21 and molecular tweezer. 22 Several studies have suggested that polyphenolic compounds reduce the risk of several degenerative diseases and exhibit in vitro inhibitory effects on amyloid formation, such as curcuminoids, resveratrol, catechin, (À)-epigallocatechin-3-gallate (EGCG) and soy isoavones.…”

Ultra‐Bright Rhodamines with Sulfobutylether‐β‐Cyclodextrin: A Viable Supramolecular Dye Laser in Aqueous Medium

“…In an earlier work, we have established stimuli‐responsive assembly of DAPI with SBE 7 βCD for on‐off fluorescent switch and controlled drug delivery applications . Of late, utilizing the recognition behavior of SBE 7 βCD towards insulin and lysozyme proteins, we have demonstrated the efficient inhibition and disintegration of amyloid fibrils from these proteins and shows promising for the treatment of amyloid related diseases . However, the host‐guest interaction studies of SBE 7 βCD with practical laser dyes and their technological applications are hardly explored.…”

“…[36] Of late, utilizing the recognition behavior of SBE 7 bCD towards insulin and lysozyme proteins, we have demonstrated the efficient inhibition and disintegration of amyloid fibrils from these proteins and shows promising for the treatment of amyloid related diseases. [37] However, the hostguest interaction studies of SBE 7 bCD with practical laser dyes and their technological applications are hardly explored. Herein, we report for the first time, the molecular details of the hostguest interaction of two technologically important rhodamine dyes, namely, rhodamine B (RhB) and rhodamine 6G (Rh6G) with SBE 7 bCD macrocyclic host in aqueous solution and project its potential to deaggregate, stabilize, and achieve enhanced fluorescence to establish an efficient laser operation in aqueous solution.…”