Inhibition and disintegration of insulin amyloid fibrils: a facile supramolecular strategy with p-sulfonatocalixarenes

Abstract

We reveal the ability of p-sulfonatocalix[4/6]arene to effectively inhibit the fibril formation in human insulin and demonstrate its potential to disintegrate the mature fibrils, a promising supramolecular strategy to combat amyloidosis.

Stimuli‐Responsive Cucurbit[7]uril‐Mediated BSA Nanoassembly for Uptake and Release of Doxorubicin

“…[2,3] Recognition-mediated nanoassembly approaches have proven very effective in camouflaging andr estoring the active protein structures, and controlling the protein misfolding and aggregation. [2,6,7] This could, in turn, preventn eurodegeneratived iseases such as Alzheimer's disease, Parkinson's disease, Prion diseases, etc. [6] An umber of synthetic macrocyclic host molecules including cyclodextrin, cucurbituril,c alixarene, etc.…”

“…[8] In ar ecent study we explored the interaction of human insulin with p-sulfonatocalixarene (SCX) macrocycles, and documented as upramolecular strategy for the inhibition and disintegration of amyloid fibrils/plaques. [7] Cucurbit[n]urils (CBn)a re relatively new additions to the repertoire of macrocyclic hosts and are an interesting class of water-soluble macrocyclic receptor molecules consisting of ah ydrophobic cavity with two identical carbonyl laced portals (Scheme 1). [9][10][11] While the hydrophobic interior provides ap otential inclusion site for nonpolar molecules, the polarizable carbonyl groupsa tt he portalsa llow the cucurbiturils to bind ions and charged molecules through ion/ charge-dipole and hydrogen bondingi nteractions bringing out dramatic photophysical changes.…”

“…[9][10][11][12][13][14] Moreover,t he electron deficient carbon centers on the periphery of the CBn provide ac rediblesite for the interaction of anionic guests. [15,16] Ta king advantage of the above attributes, few groups have shownt he interaction of cucurbit [7]uril( CB7) and cucurbit [8]uril (CB8) with aminoacids, polypeptides and small proteins such as insulin. [17][18][19] Kim et al have shown inhibition in the amyloid fibrillation of insulin and Ab40 peptides by encapsulating the active phenylalanine groupsu sing cucurbit [7]uril (CB7).…”

“…[15,16] Ta king advantage of the above attributes, few groups have shownt he interaction of cucurbit [7]uril( CB7) and cucurbit [8]uril (CB8) with aminoacids, polypeptides and small proteins such as insulin. [17][18][19] Kim et al have shown inhibition in the amyloid fibrillation of insulin and Ab40 peptides by encapsulating the active phenylalanine groupsu sing cucurbit [7]uril (CB7). [6] Earlier,w ed emonstrated an enhancer strategy using CB7, bovine serum albumin (BSA) and at riphenylmethane (TPM) dye, malachite green, through cooperative binding.…”

The Discovery of the Effect of closo‐Borate on Amyloid Fibril Formation

“…Most of the reported compounds that inhibit protein fibril formation are small organic molecules, including aromatic‐rich compounds (polyphenolic compounds, benzaldehyde derivatives, benzoxazoles). Besides, among compounds with anti‐fibrillogenic activity the heme‐like macrocycles porphyrines and phthalocyanines, β‐cyclodextrin, p ‐sulfonatocalix[4/6]arene were described. We have previously discovered the ability of macrocyclic metal complexes – axially‐coordinated phthalocyanines and iron(II) clathrochelates to inhibit the fibrillization or change the morphology of formed protein aggregates.…”