Monika Holubová , Juraj Kronek , Shubhashis Datta , Volodymyr Lobaz , Jiřina Hromádková , Petr Štěpánek , Martin Hrubý
{"title":"两亲性(双)梯度共聚(2-恶唑啉)是有效的淀粉样纤维形成抑制剂。","authors":"Monika Holubová , Juraj Kronek , Shubhashis Datta , Volodymyr Lobaz , Jiřina Hromádková , Petr Štěpánek , Martin Hrubý","doi":"10.1016/j.colsurfb.2023.113521","DOIUrl":null,"url":null,"abstract":"<div><p><em>Motivation:</em></p><p>Amyloidoses<span> are diseases caused by the accumulation of normally soluble proteins in the form of insoluble amyloids, leading to the gradual dysfunction and failure of various organs and tissues. Inhibiting amyloid formation is therefore an important therapeutic target.</span></p><p><em>Hypothesis:</em></p><p><span>We hypothesized that mono- and di-gradient amphiphilic copolymers of hydrophilic 2-(m)ethyl-2-oxazoline and hydrophobic 2-aryl-2-oxazolines may inhibit </span>amyloid fibril formation.</p><p><em>Experiments:</em></p><p><span><span>In the model system with hen egg white lysozyme (HEWL) as amyloidogenic protein we determined the effect of these polymers on the amyloid formation by making use of the </span>thioflavin<span> T fluorescence, transmission electron microscopy, </span></span>isothermal titration calorimetry<span>, and dynamic light scattering.</span></p><p><em>Findings:</em></p><p>We found that some gradient copolymers possess very potent concentration-dependent inhibitory effects on HEWL amyloid formation. Structure-activity relationship revealed that copolymers with higher ratios of aromatic monomeric units had stronger amyloid suppression effects, most plausibly due to the combination of hydrophobic and π-π interactions. The measurements also revealed that the polymers that inhibit amyloid formation most plausibly do so in the form of micelles that interact with the growing amyloid fibril ends, not with isolated HEWL molecules in solution. These findings suggest the potential use of these gradient copolymers as therapeutic agents for amyloidoses.</p></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"230 ","pages":"Article 113521"},"PeriodicalIF":5.4000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Amphiphilic (di-)gradient copoly(2-oxazoline)s are potent amyloid fibril formation inhibitors\",\"authors\":\"Monika Holubová , Juraj Kronek , Shubhashis Datta , Volodymyr Lobaz , Jiřina Hromádková , Petr Štěpánek , Martin Hrubý\",\"doi\":\"10.1016/j.colsurfb.2023.113521\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><em>Motivation:</em></p><p>Amyloidoses<span> are diseases caused by the accumulation of normally soluble proteins in the form of insoluble amyloids, leading to the gradual dysfunction and failure of various organs and tissues. Inhibiting amyloid formation is therefore an important therapeutic target.</span></p><p><em>Hypothesis:</em></p><p><span>We hypothesized that mono- and di-gradient amphiphilic copolymers of hydrophilic 2-(m)ethyl-2-oxazoline and hydrophobic 2-aryl-2-oxazolines may inhibit </span>amyloid fibril formation.</p><p><em>Experiments:</em></p><p><span><span>In the model system with hen egg white lysozyme (HEWL) as amyloidogenic protein we determined the effect of these polymers on the amyloid formation by making use of the </span>thioflavin<span> T fluorescence, transmission electron microscopy, </span></span>isothermal titration calorimetry<span>, and dynamic light scattering.</span></p><p><em>Findings:</em></p><p>We found that some gradient copolymers possess very potent concentration-dependent inhibitory effects on HEWL amyloid formation. Structure-activity relationship revealed that copolymers with higher ratios of aromatic monomeric units had stronger amyloid suppression effects, most plausibly due to the combination of hydrophobic and π-π interactions. The measurements also revealed that the polymers that inhibit amyloid formation most plausibly do so in the form of micelles that interact with the growing amyloid fibril ends, not with isolated HEWL molecules in solution. These findings suggest the potential use of these gradient copolymers as therapeutic agents for amyloidoses.</p></div>\",\"PeriodicalId\":279,\"journal\":{\"name\":\"Colloids and Surfaces B: Biointerfaces\",\"volume\":\"230 \",\"pages\":\"Article 113521\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Colloids and Surfaces B: Biointerfaces\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0927776523003995\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOPHYSICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Colloids and Surfaces B: Biointerfaces","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0927776523003995","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOPHYSICS","Score":null,"Total":0}
Amphiphilic (di-)gradient copoly(2-oxazoline)s are potent amyloid fibril formation inhibitors
Motivation:
Amyloidoses are diseases caused by the accumulation of normally soluble proteins in the form of insoluble amyloids, leading to the gradual dysfunction and failure of various organs and tissues. Inhibiting amyloid formation is therefore an important therapeutic target.
Hypothesis:
We hypothesized that mono- and di-gradient amphiphilic copolymers of hydrophilic 2-(m)ethyl-2-oxazoline and hydrophobic 2-aryl-2-oxazolines may inhibit amyloid fibril formation.
Experiments:
In the model system with hen egg white lysozyme (HEWL) as amyloidogenic protein we determined the effect of these polymers on the amyloid formation by making use of the thioflavin T fluorescence, transmission electron microscopy, isothermal titration calorimetry, and dynamic light scattering.
Findings:
We found that some gradient copolymers possess very potent concentration-dependent inhibitory effects on HEWL amyloid formation. Structure-activity relationship revealed that copolymers with higher ratios of aromatic monomeric units had stronger amyloid suppression effects, most plausibly due to the combination of hydrophobic and π-π interactions. The measurements also revealed that the polymers that inhibit amyloid formation most plausibly do so in the form of micelles that interact with the growing amyloid fibril ends, not with isolated HEWL molecules in solution. These findings suggest the potential use of these gradient copolymers as therapeutic agents for amyloidoses.
期刊介绍:
Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields.
Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication.
The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.