The Investigation on Resorcinarenes towards either Inhibiting or Promoting Insulin Fibrillation

Han, Xu; Tian, Chuan; Gandra, Ingrid; Eslava, Valeria J.; Galindres, Diana M.; Vargas, Édgar F.; Leblanc, Roger M.

doi:10.1002/chem.201704932

Cited by 15 publications

(10 citation statements)

References 31 publications

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“…More recently, the same research group studied the effects of different tail-engineered resorcinarenes on the aggregation of insulin. [75] The resorcinarene itself exerts a strong inhibitory effect on insulin at a ratio of 1:0.2 (insulin:resorcinarene). However, changing the tail from F I G U R E 6 Molecular structures of the calixarenes reported to modulate the aggregation of amyloid proteins thiomethyl to propyl or butyl results in disappearance of the inhibitory effect.…”

Section: Cas For Modulating Amyloid Aggregationmentioning

confidence: 99%

Modulating the aggregation of amyloid proteins by macrocycles

2022

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The aggregation of amyloid proteins has been suggested to be the main cause of multiple human disorders; for example, amyloid β aggregates in Alzheimer's disease and α-synuclein aggregates in Parkinson's disease. In the search for therapeutic medicines, many molecules have been discovered and developed to modulate the aggregation of amyloid proteins. This century has witnessed the flourishing growth of supramolecular chemistry, and some biocompatible macrocycles have been proven to inhibit the aggregation of some amyloid proteins via host-guest interactions and could thus be used for the prevention or treatment of related diseases. Here, we review the application of macrocycles in modulating the aggregation of amyloid proteins.

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Section: Cas For Modulating Amyloid Aggregationmentioning

confidence: 99%

Modulating the aggregation of amyloid proteins by macrocycles

2022

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“…[115] The investigation by Xu et al on resorcinarene, a polyphenolic cyclic oligomer, revealed its potential towards inhibiting insulin fibrillation and serves as a new strategy towards maintaining insulin stability. [120] Length of engineered tails of such resorcinarene derivatives play a pivotal role with respect to its inhibitory efficacy. Moreover, many reports have described the inhibitory efficacy of cyclodextrin in insulin fibrillation through electrostatic and hydrophobic interactions.…”

Section: Other Additivesmentioning

confidence: 99%

Strategies for Interference of Insulin Fibrillogenesis: Challenges and Advances

et al. 2022

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The discovery of insulin came with very high hopes for diabetic patients. In 2021, the world celebrated the 100th anniversary of the discovery of this vital hormone. However, external use of insulin is highly affected by its aggregating tendency that occurs during its manufacturing, transportation, and improper handling which ultimately leads to its pharmaceutically and biologically ineffective form. In this review, we aim to discuss the various approaches used for decelerating insulin aggregation which results in the enhancement of its overall structural stability and usage. The approaches that are discussed are broadly classified as either a measure through excipient additions or by intrinsic modifications in the insulin native structure.

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“…We then employed solid-state NMR to further confirm that GCA and CD were coassembled. Compared with GCA + CD, the benzene 13 C peak of GCA-CD underwent a downfield shift (Supporting Information Figure S2), thereby indicating that GCA interacted with CD in the GCA-CD coassembly. Having confirmed the formation of the GCA-CD coassembly, we validated whether these two kinds of macrocycles were evenly distributed on the surface of the coassembly or self-sorted each other to generate microphase separation by using energydispersive spectrometry-elemental mapping analysis.…”

Section: Construction and Characterization Of The Gca-cd Coassembly Of Heteromultivalent Recognitionmentioning

confidence: 99%

“…For example, natural small molecules, such as curcumin and congo red, have been reported to interact with the fibril-related conformation, and thus affect protein aggregation. 8 Artificial receptors, such as molecular tweezer, 9 cyclodextrin, 10,11 calixarene, 12 resorcinarene, 13,14 and cucurbituril, 15 have been designed to bind with one or several certain amino acids and inhibit the fibrillation of proteins. Certain peptides, either designed directly based on the Aβ sequence or designed without relying on the sequence, may also be utilized as inhibitors to interfere with the formation of fibrils or disrupt the aggregation process.…”

Section: Introductionmentioning

confidence: 99%

Coassembly of Macrocyclic Amphiphiles for Anti-β-Amyloid Therapy of Alzheimer’s Disease

Pan

Wang

et al. 2021

CCS Chem

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Based on the amyloid hypothesis, anti-β-amyloid (Aβ) therapy has dominated clinical trials for the prevention and treatment of Alzheimer's disease (AD) in recent years. A key element of this strategy is the interaction between therapeutic agents and Aβ. However, the design and development of artificial receptors that may render selective and strong recognition toward Aβ remains a huge challenge because of the complexity and size of peptide guests and their flexible conformation. To address this issue, we fabricated a coassembly of two kinds of macrocyclic amphiphiles, guanidinium-modified calixarene (GCA) and cyclodextrin (CD). The GCA-CD coassembly exhibited extraordinarily strong binding affinity to Aβ with exquisite specificity benefiting from the heteromultivalent recognition. As a result, GCA-CD was capable of completely inhibiting the fibrillation of Aβ and disintegrating mature fibrils, and moreover, effectively mitigated the cytotoxicity induced by Aβ fibrils and improved the cognitive deficit of AD mice.The potential of GCA-CD as a therapeutic agent for the treatment of AD was witnessed both in vitro and in vivo.

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The Investigation on Resorcinarenes towards either Inhibiting or Promoting Insulin Fibrillation

Cited by 15 publications

References 31 publications

Modulating the aggregation of amyloid proteins by macrocycles

Modulating the aggregation of amyloid proteins by macrocycles

Strategies for Interference of Insulin Fibrillogenesis: Challenges and Advances

Coassembly of Macrocyclic Amphiphiles for Anti-β-Amyloid Therapy of Alzheimer’s Disease

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