Aminocyclodextrin Oligomers as Protective Agents of Protein Aggregation

Abstract

Over 30 different amyloid proteins and a number of corresponding protein‐misfolding diseases have been identified. Among these is Alzheimer's disease, the most common neurodegenerative disorder. The treatment of these diseases is still a goal to reach and many molecules have been studied in this context. Among these, the cyclodextrins have shown interesting potential as agents against protein aggregation (antiaggregants). On the basis of this interest, we investigated the effect on protein aggregation of some oligomers of β‐cyclodextrins. In particular, it was found that amino oligomers show good inhibition of β‐amyloid aggregation in the micromolar concentration range. The presence of both a multicavity system and amino groups seems to be essential for preventing protein aggregation.

Harnessing Polyisobutylene by Rotaxanation with γ‐Cyclodextrin: Opportunities for Making Smart Molecular Necklaces

“…Nevertheless, the low solubility of CD‐based PR in pure polar solvents such as water, methanol, or acetonitrile exhibiting both high molecular weight and polydispersity constitutes a major bottleneck for their mass spectrometry characterization. Nonetheless, SEC and NMR are the widest used techniques for CD‐based superstructure analysis, and particularly MALDI‐TOF mass spectrometry has proven that it can advantageously reinforce the arsenal of available characterization tools . Detailed MALDI‐TOF MS analysis was obtained confirming the presence of γ‐CDs threaded on the PIB chain, but more importantly confirming the blocking reaction ensuring efficient formation of the polyrotaxane.…”

“…Nonetheless, SEC and NMR are the widest used techniques for CD-based superstructure analysis, and particularly MALDI-TOF mass spectrometry has proven that it can advantageously reinforce the arsenal of available characterization tools. [29][30][31]35,36] Detailed MALDI-TOF MS analysis was obtained confirming the presence of γ-CDs threaded on the PIB chain, but more importantly confirming the blocking reaction ensuring efficient formation of the polyrotaxane. A typical MALDI-TOF mass spectrum exhibiting ions in the range of m/z 3000−19 600 with an average of 1300−1500 mass units shifts corresponding to the unmodified, mono-, or disulfated γ-CD molecular weights (Figure 5A).…”

Cyclodextrin Nanoparticles Bearing 8‐Hydroxyquinoline Ligands as Multifunctional Biomaterials

“…As for the aggregation of Ab 1-42 alone, the lag phase lasts 19.0 hours and the maximum fluorescenceg ain (F max ÀF 0 ) reachesavalue of 13.9, confirming the kinetic behavior previously reported. [21] The effect of pCDHQ on Ab aggregation is concentration dependent. When pCDHQ is equimolar to Ab 1-42 , F max ÀF 0 value is markedly lower than that fitted for Ab 1-42 alone (2.4 vs. 13.9) and t lag is doubled (39.0 vs. 19.0) showing ar etarding effect of pCDHQ on the aggregation; t 1/2 is also affected by the presence of pCDHQ, though the variation is lower than those observedf or F max ÀF 0 and t lag .I ncreasingt he pCDHQ/Ab molar ratio (2:1 and 5:1), the amyloid aggregation is completely inhibited.…”

“…[13] Dynamiclight scattering measurements DLS measurements were carried out using aZ etasizer Nano ZS (Malvern Instruments, UK) equipped for backscattering at 1738 with a6 33 nm He-Ne laser.E ach DLS measurement was run as reported elsewhere. [14,21] Trolox equivalent antioxidant capacity assay TEAC values were determined by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation decolor- ization assay using 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), as reported elsewhere. [13] Synthesis of pCDHQ EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, 23 mg, 0.122 mmol) and NHS (N-hydroxysuccinimide, 15 mg, 0.122 mmol) were added to an aqueous solution (10 mL) of pACD (100 mg, 1.14 10 À3 mmol).…”

“…[18][19][20] Moreover,o ligomers and polymers of CDs have shown noteworthyc apacity in inhibiting protein aggregation. [21] Notwithstandingt he abundance of CDs polymers studied, metal-chelating polymers basedo nC Ds have been poorly explored. The few exampleso fC Dp olymers with metal chelating properties have been employed for removing metal ions from plasticized membranes or aqueous solution.…”