Inhibition of Insulin Amyloid Fibrillogenesis Using Antioxidant Copolymers with Dopamine Pendants

IF 12.1 2区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Small Pub Date : 2025-03-20 DOI:10.1002/smll.202501206
Tamanna Mallick, Anushree Mondal, Shubham Das, Priyadarsi De
{"title":"Inhibition of Insulin Amyloid Fibrillogenesis Using Antioxidant Copolymers with Dopamine Pendants","authors":"Tamanna Mallick,&nbsp;Anushree Mondal,&nbsp;Shubham Das,&nbsp;Priyadarsi De","doi":"10.1002/smll.202501206","DOIUrl":null,"url":null,"abstract":"<p>Amyloid aggregation, intricately related to various neurodegenerative and metabolic diseases, presents a significant growing health challenge. Dopamine, a potent antioxidant, plays a pivotal role in modulating protein misfolding by leveraging its potent anti-amyloidogenic and neuroprotective properties. However, its biological applications are limited by poor aqueous solubility and suboptimal biocompatibility. To address these challenges, water-soluble copolymers (<b>DP1</b>-<b>DP3</b>) featuring dopamine and glucose side-chain pendants are fabricated and investigated for their efficacy in inhibiting amyloid fibril formation from insulin and amyloid beta (A<i>β</i><sub>42</sub>) peptide. The effects of <b>DP1</b>-<b>DP3</b> copolymers on amyloid fibrillation are assessed using several biophysical techniques, which demonstrate excellent radical scavenging properties and the remarkable efficacy of <b>DP3</b> copolymer in suppressing insulin amyloid fibrillation, achieving ≈97% inhibition. Isothermal titration calorimetry (ITC) and fluorescence binding experiments are carried out to quantify the insulin-<b>DP3</b> complex formation. Molecular dynamics simulations validate the ability of <b>DP3</b> to prevent amyloid fibrillogenesis of both insulin and A<i>β</i><sub>42</sub>. These studies demonstrate beneficial interactions between <b>DP3</b> and amyloidogenic protein/peptide, facilitating the stability of the resulting complexes. Overall, the present findings suggest that dopamine-based antioxidant polymers hold significant potential as advanced therapeutic agents for preventing amyloidogenic disorders.</p>","PeriodicalId":228,"journal":{"name":"Small","volume":"21 18","pages":""},"PeriodicalIF":12.1000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Small","FirstCategoryId":"88","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/smll.202501206","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

Abstract

Amyloid aggregation, intricately related to various neurodegenerative and metabolic diseases, presents a significant growing health challenge. Dopamine, a potent antioxidant, plays a pivotal role in modulating protein misfolding by leveraging its potent anti-amyloidogenic and neuroprotective properties. However, its biological applications are limited by poor aqueous solubility and suboptimal biocompatibility. To address these challenges, water-soluble copolymers (DP1-DP3) featuring dopamine and glucose side-chain pendants are fabricated and investigated for their efficacy in inhibiting amyloid fibril formation from insulin and amyloid beta (Aβ42) peptide. The effects of DP1-DP3 copolymers on amyloid fibrillation are assessed using several biophysical techniques, which demonstrate excellent radical scavenging properties and the remarkable efficacy of DP3 copolymer in suppressing insulin amyloid fibrillation, achieving ≈97% inhibition. Isothermal titration calorimetry (ITC) and fluorescence binding experiments are carried out to quantify the insulin-DP3 complex formation. Molecular dynamics simulations validate the ability of DP3 to prevent amyloid fibrillogenesis of both insulin and Aβ42. These studies demonstrate beneficial interactions between DP3 and amyloidogenic protein/peptide, facilitating the stability of the resulting complexes. Overall, the present findings suggest that dopamine-based antioxidant polymers hold significant potential as advanced therapeutic agents for preventing amyloidogenic disorders.

Abstract Image

Abstract Image

含多巴胺悬垂的抗氧化共聚物抑制胰岛素淀粉样蛋白纤维形成
淀粉样蛋白聚集与各种神经退行性和代谢性疾病有着复杂的关系,对健康提出了重大的挑战。多巴胺是一种有效的抗氧化剂,通过利用其有效的抗淀粉样变性和神经保护特性,在调节蛋白质错误折叠中起关键作用。然而,其生物应用受到水溶性差和生物相容性欠佳的限制。为了解决这些挑战,制备了具有多巴胺和葡萄糖侧链垂坠的水溶性共聚物(DP1-DP3),并研究了其抑制胰岛素和淀粉样蛋白β (Aβ42)肽形成淀粉样蛋白纤维的功效。DP1-DP3共聚物对淀粉样蛋白纤颤的影响通过几种生物物理技术进行了评估,结果表明DP3共聚物具有优异的自由基清除性能,对胰岛素淀粉样蛋白纤颤的抑制效果显著,达到约97%。采用等温滴定量热法(ITC)和荧光结合实验来定量胰岛素- dp3复合物的形成。分子动力学模拟验证了DP3阻止胰岛素和a - β42淀粉样蛋白纤维形成的能力。这些研究证明了DP3和淀粉样蛋白/肽之间有益的相互作用,促进了所产生复合物的稳定性。总的来说,目前的研究结果表明,以多巴胺为基础的抗氧化聚合物作为预防淀粉样变性疾病的先进治疗剂具有巨大的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Small
Small 工程技术-材料科学:综合
CiteScore
17.70
自引率
3.80%
发文量
1830
审稿时长
2.1 months
期刊介绍: Small serves as an exceptional platform for both experimental and theoretical studies in fundamental and applied interdisciplinary research at the nano- and microscale. The journal offers a compelling mix of peer-reviewed Research Articles, Reviews, Perspectives, and Comments. With a remarkable 2022 Journal Impact Factor of 13.3 (Journal Citation Reports from Clarivate Analytics, 2023), Small remains among the top multidisciplinary journals, covering a wide range of topics at the interface of materials science, chemistry, physics, engineering, medicine, and biology. Small's readership includes biochemists, biologists, biomedical scientists, chemists, engineers, information technologists, materials scientists, physicists, and theoreticians alike.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信