Tamanna Mallick, Anushree Mondal, Shubham Das, Priyadarsi De
{"title":"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","authors":"Tamanna Mallick, Anushree Mondal, Shubham Das, 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":"{\"title\":\"Inhibition of Insulin Amyloid Fibrillogenesis Using Antioxidant Copolymers with Dopamine Pendants\",\"authors\":\"Tamanna Mallick, Anushree Mondal, Shubham Das, 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}","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}
Inhibition of Insulin Amyloid Fibrillogenesis Using Antioxidant Copolymers with Dopamine Pendants
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.
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.