Biophysical characterization of glatiramer acetate (Copaxone): membrane model interactions, vesicle leakage, and secondary structure effects

Biophysical characterization of glatiramer acetate (Copaxone): membrane model interactions, vesicle leakage, and secondary structure effects | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Biophysical characterization of glatiramer acetate (Copaxone): membrane model interactions, vesicle leakage, and secondary structure effects Jüri Jarvet, Elina Berntsson, Fatemeh Madani, Jinghui Luo, Astrid Gräslund, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8138862/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The synthetic copolymer glatiramer acetate (GA), commercially known as Copaxone, was developed in the 1990s as a treatment for relapsing multiple sclerosis (MS). Recent studies suggest that GA may also exhibit antimicrobial activity. Despite its long-standing clinical use, the molecular mechanism of GA remains poorly understood. Elucidating these mechanisms could facilitate drug repurposing and provide insights into the molecular basis of MS pathology. Here, we employed a range of biophysical techniques to characterize the structural and interaction properties of GA, focusing on its behavior in membrane-mimicking environments such as micelles and large unilamellar vesicles (LUVs). Our results show that GA induces membrane leakage in anionic LUVs, and that GA adopts temperature-dependent secondary structure conformations ranging from α-helical to random coil, which are further influenced by interactions with micelles of different charge. Additionally, GA peptides exhibit an average hydrodynamic radius of approximately 3 nm, and predominantly exist in aggregated rather than monomeric forms. These results highlight the complex structural dynamics of GA and suggest that its biological activity may be closely linked to membrane interactions and peptide aggregation. Peptide Neurodegeneration Spectroscopy Drug mechanism Amyloid disease Full Text Additional Declarations The authors declare potential competing interests as follows: The authors declare no competing interests. J.J., E.B., A.G., and S.K.T.S.W. are shareholders of CellPept Sweden AB. Neither this company, nor the funding organizations, had any role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Supplementary Files CopaxoneSINov2025.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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J.J., E.B., A.G., and S.K.T.S.W. are shareholders of CellPept Sweden AB. Neither this company, nor the funding organizations, had any role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eBiophysical characterization of glatiramer acetate (Copaxone): membrane model interactions, vesicle leakage, and secondary structure effects\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Stockholm University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Peptide, Neurodegeneration, Spectroscopy, Drug mechanism, Amyloid disease","lastPublishedDoi":"10.21203/rs.3.rs-8138862/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8138862/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe synthetic copolymer glatiramer acetate (GA), commercially known as Copaxone, was developed in the 1990s as a treatment for relapsing multiple sclerosis (MS). Recent studies suggest that GA may also exhibit antimicrobial activity. Despite its long-standing clinical use, the molecular mechanism of GA remains poorly understood. Elucidating these mechanisms could facilitate drug repurposing and provide insights into the molecular basis of MS pathology.\u003c/p\u003e\u003cp\u003eHere, we employed a range of biophysical techniques to characterize the structural and interaction properties of GA, focusing on its behavior in membrane-mimicking environments such as micelles and large unilamellar vesicles (LUVs). Our results show that GA induces membrane leakage in anionic LUVs, and that GA adopts temperature-dependent secondary structure conformations ranging from α-helical to random coil, which are further influenced by interactions with micelles of different charge. 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