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The spreading of aggregated \u03b1Syn between neurons is at least partly dependent on electrostatic interactions between positively charged stretches on \u03b1Syn fibrils and the negatively charged heparan sulphate proteoglycans on the cell surface. To date there is still no therapeutic option available that could halt the progression of Parkinson\u2019s disease and one of the major limitations is likely the relatively low proportion of \u03b1Syn aggregates accessible to drugs in the extracellular space. Here, we investigated whether a negatively charged peptide tail fused to the \u03b1Syn aggregate-specific antibodies SynO2 and 9E4 could enhance the antibodies\u2019 avidity to \u03b1Syn aggregates in order to improve their potential therapeutic effect through inhibiting cell-to-cell spreading and enhancing the clearance of extracellular aggregates. We performed ELISAs to test the avidity to \u03b1Syn aggregates of both monovalent and bivalent antibody formats with and without the peptide tail. Our results show that the addition of the negatively charged peptide tail decreased the binding strength of both antibodies to \u03b1Syn aggregates at physiological salt conditions, which can likely be explained by intermolecular repulsions between the tail and the negatively charged C-terminus of \u03b1Syn. Additionally, the tail might interact with the paratopes of the SynO2 antibody abolishing its binding to \u03b1Syn aggregates. Conclusively, our peptide tail did not fulfil the required characteristics to improve the antibodies\u2019 binding to \u03b1Syn aggregates. Fine-tuning the design of the peptide tail to avoid its interaction with the antibodies\u2019 CDR and to better mimic relevant characteristics of heparan sulphates for \u03b1Syn aggregate binding may help overcome the limitations observed in this study.<\/jats:p>","DOI":"10.1371\/journal.pone.0308521","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T19:19:29Z","timestamp":1724959169000},"page":"e0308521","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A charged tail on anti-\u03b1-Synuclein antibodies does not enhance their affinity to \u03b1-Synuclein fibrils"],"prefix":"10.1371","volume":"19","author":[{"given":"Inga","family":"Petersen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Godec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farahnaz","family":"Ranjbarian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-2957","authenticated-orcid":true,"given":"Anders","family":"Hofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Mirabello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-6792","authenticated-orcid":true,"given":"Greta","family":"Hultqvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"pone.0308521.ref001","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1749-6632.2000.tb06900.x","article-title":"The \u03b1\u2010Synucleinopathies: Parkinson\u2019s Disease, Dementia with Lewy Bodies, and Multiple System Atrophy","volume":"920","author":"MG Spillantini","year":"2000","journal-title":"Annals of the New York Academy of Sciences"},{"key":"pone.0308521.ref002","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s42003-018-0049-z","article-title":"Structural insights from lipid-bilayer nanodiscs link \u03b1-Synuclein membrane-binding modes to amyloid fibril formation","volume":"1","author":"T Viennet","year":"2018","journal-title":"Commun Biol"},{"key":"pone.0308521.ref003","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.1073\/pnas.0809232106","article-title":"Interplay of \u03b1-synuclein binding and conformational switching probed by single-molecule fluorescence","volume":"106","author":"ACM Ferreon","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0308521.ref004","doi-asserted-by":"crossref","first-page":"15313","DOI":"10.1074\/jbc.M213128200","article-title":"A Broken \u03b1-Helix in Folded \u03b1-Synuclein","volume":"278","author":"S Chandra","year":"2003","journal-title":"Journal of Biological Chemistry"},{"key":"pone.0308521.ref005","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0022-2836(03)00520-5","article-title":"A Structural and Functional Role for 11-mer Repeats in \u03b1-Synuclein and Other Exchangeable Lipid Binding Proteins","volume":"329","author":"R Bussell","year":"2003","journal-title":"Journal of Molecular Biology"},{"key":"pone.0308521.ref006","doi-asserted-by":"crossref","first-page":"167714","DOI":"10.1016\/j.jmb.2022.167714","article-title":"Functional and Pathological Effects of \u03b1-Synuclein on Synaptic SNARE Complexes","volume":"435","author":"V Gao","year":"2023","journal-title":"Journal of Molecular Biology"},{"key":"pone.0308521.ref007","doi-asserted-by":"crossref","first-page":"e1867","DOI":"10.1371\/journal.pone.0001867","article-title":"Formation of Toxic Oligomeric \u03b1-Synuclein Species in Living Cells.","volume":"3","author":"TF Outeiro","year":"2008","journal-title":"PLoS ONE."},{"key":"pone.0308521.ref008","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1038\/s41467-021-21937-3","article-title":"The release of toxic oligomers from \u03b1-synuclein fibrils induces dysfunction in neuronal cells.","volume":"12","author":"R Cascella","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0308521.ref009","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.1073\/pnas.1100976108","article-title":"In vivo demonstration that -synuclein oligomers are toxic","volume":"108","author":"B Winner","year":"2011","journal-title":"Proceedings of the National Academy of Sciences"},{"journal-title":"Front Neurosci","article-title":"Alpha-Synuclein Oligomers\u2014Neurotoxic Molecules in Parkinson\u2019s Disease and Other Lewy Body Disorders.","author":"M. 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Dis"},{"key":"pone.0308521.ref032","doi-asserted-by":"crossref","first-page":"6838","DOI":"10.1523\/JNEUROSCI.5699-09.2010","article-title":"Cell-Produced -Synuclein Is Secreted in a Calcium-Dependent Manner by Exosomes and Impacts Neuronal Survival","volume":"30","author":"E Emmanouilidou","year":"2010","journal-title":"Journal of Neuroscience"},{"key":"pone.0308521.ref033","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1096\/fj.10-164624","article-title":"Heat-shock protein 70 modulates toxic extracellular \u03b1-synuclein oligomers and rescues trans-synaptic toxicity","volume":"25","author":"KM Danzer","year":"2011","journal-title":"FASEB J"},{"key":"pone.0308521.ref034","doi-asserted-by":"crossref","first-page":"e0153020","DOI":"10.1371\/journal.pone.0153020","article-title":"Direct Observation of \u03b1-Synuclein Amyloid Aggregates in Endocytic Vesicles of Neuroblastoma Cells.","volume":"11","author":"MM Apetri","year":"2016","journal-title":"PLoS One"},{"key":"pone.0308521.ref035","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13024-020-00368-6","article-title":"Initiation and propagation of \u03b1-synuclein aggregation in the nervous system.","volume":"15","author":"BA Hijaz","year":"2020","journal-title":"Mol Neurodegener."},{"key":"pone.0308521.ref036","article-title":"Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds","author":"BB Holmes","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0308521.ref037","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1021\/acschemneuro.9b00562","article-title":"Correlation between Cellular Uptake and Cytotoxicity of Fragmented \u03b1-Synuclein Amyloid Fibrils Suggests Intracellular Basis for Toxicity","volume":"11","author":"X Zhang","year":"2020","journal-title":"ACS Chem Neurosci"},{"key":"pone.0308521.ref038","doi-asserted-by":"crossref","first-page":"9008","DOI":"10.1038\/s41598-017-08720-5","article-title":"Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type","volume":"7","author":"E Ihse","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0308521.ref039","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.3390\/ijms19124129","article-title":"Extracellular Interactions of Alpha-Synuclein in Multiple System Atrophy.","volume":"19","author":"D Valdinocci","year":"2018","journal-title":"Int J Mol Sci."},{"key":"pone.0308521.ref040","doi-asserted-by":"crossref","first-page":"aah3374","DOI":"10.1126\/science.aah3374","article-title":"Pathological \u03b1-synuclein transmission initiated by binding lymphocyte-activation gene 3","volume":"353","author":"X Mao","year":"2016","journal-title":"Science"},{"key":"pone.0308521.ref041","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.celrep.2017.12.009","article-title":"Prion-like Propagation of \u03b1-Synuclein Is Regulated by the Fc\u03b3RIIB-SHP-1\/2 Signaling Pathway in Neurons.","volume":"22","author":"YR Choi","year":"2018","journal-title":"Cell Reports"},{"key":"pone.0308521.ref042","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1046\/j.1471-4159.1999.721681.x","article-title":"The Sulfate Moieties of Glycosaminoglycans Are Critical for the Enhancement of \u03b2\u2010Amyloid Protein Fibril Formation","volume":"72","author":"GM Castillo","year":"1999","journal-title":"Journal of Neurochemistry"},{"key":"pone.0308521.ref043","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1021\/bi011711s","article-title":"Heparin and Other Glycosaminoglycans Stimulate the Formation of Amyloid Fibrils from \u03b1-Synuclein in Vitro","volume":"41","author":"JA Cohlberg","year":"2002","journal-title":"Biochemistry"},{"key":"pone.0308521.ref044","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/383550a0","article-title":"Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans","volume":"383","author":"M Goedert","year":"1996","journal-title":"Nature"},{"key":"pone.0308521.ref045","doi-asserted-by":"crossref","first-page":"5584","DOI":"10.1073\/pnas.1101194108","article-title":"Heparan sulfate\/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein","volume":"108","author":"F Noborn","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0308521.ref046","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/emboj\/20.3.377","article-title":"\u2018n. Sulfated glycans and elevated temperature stimulate PrPSc-dependent cell-free formation of protease-resistant prion protein","volume":"20","author":"C Wong","year":"2001","journal-title":"The EMBO Journal"},{"key":"pone.0308521.ref047","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-biochem-060713-035314","article-title":"Demystifying heparan sulfate-protein interactions","volume":"83","author":"D Xu","year":"2014","journal-title":"Annu Rev Biochem"},{"key":"pone.0308521.ref048","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.neurobiolaging.2006.02.015","article-title":"Targeting soluble A\u03b2 peptide with Tramiprosate for the treatment of brain amyloidosis","volume":"28","author":"F Gervais","year":"2007","journal-title":"Neurobiology of Aging"},{"key":"pone.0308521.ref049","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.1523\/JNEUROSCI.0550-04.2004","article-title":"Peripheral Treatment with Enoxaparin, a Low Molecular Weight Heparin, Reduces Plaques and \u03b2-Amyloid Accumulation in a Mouse Model of Alzheimer\u2019s Disease","volume":"24","author":"L Bergamaschini","year":"2004","journal-title":"J Neurosci"},{"key":"pone.0308521.ref050","first-page":"jnc.15768","article-title":"A single chain fragment constant (scFc) design enables easy production of a monovalent BBB transporter and provides an improved brain uptake at elevated doses.","author":"JI Morrison","year":"2023","journal-title":"Journal of Neurochemistry"},{"key":"pone.0308521.ref051","article-title":"The PyMOL Molecular Graphics System, version 3.0.3","author":"LLC Schr\u00f6dinger","year":"2010","journal-title":"Schr\u00f6dinger, LLC"},{"key":"pone.0308521.ref052","doi-asserted-by":"crossref","first-page":"2256668","DOI":"10.1080\/19420862.2023.2256668","article-title":"Multivalent design of the monoclonal SynO2 antibody improves binding strength to soluble \u03b1-Synuclein aggregates.","volume":"15","author":"I Petersen","year":"2023","journal-title":"mAbs."},{"key":"pone.0308521.ref053","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40035-021-00258-x","article-title":"Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta","volume":"10","author":"F Rofo","year":"2021","journal-title":"Transl Neurodegener"},{"key":"pone.0308521.ref054","article-title":"A Brain-Targeting Bispecific-Multivalent Antibody Clears Soluble Amyloid-Beta Aggregates in Alzheimer\u2019s Disease Mice.","author":"F Rofo","year":"2022","journal-title":"Neurotherapeutics"},{"key":"pone.0308521.ref055","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1369\/0022155417740881","article-title":"The Role of Heparan Sulfate in Inflammation, and the Development of Biomimetics as Anti-Inflammatory Strategies","volume":"66","author":"BL Farrugia","year":"2018","journal-title":"J Histochem Cytochem"},{"key":"pone.0308521.ref056","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s12974-023-02925-4","article-title":"The novel HS-mimetic, Tet-29, regulates immune cell trafficking across barriers of the CNS during inflammation","volume":"20","author":"T Peck","year":"2023","journal-title":"J Neuroinflammation"},{"key":"pone.0308521.ref057","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1021\/acscentsci.1c01293","article-title":"Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike\u2013ACE2 Interaction.","volume":"8","author":"SE Guimond","year":"2022","journal-title":"ACS Cent Sci."},{"key":"pone.0308521.ref058","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.3390\/molecules23112915","article-title":"Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity.","volume":"23","author":"C Lanzi","year":"2018","journal-title":"Molecules"},{"key":"pone.0308521.ref059","doi-asserted-by":"crossref","first-page":"7080","DOI":"10.1021\/acsami.0c20744","article-title":"Inhibition of Tumor\u2013Host Cell Interactions Using Synthetic Heparin Mimetics.","volume":"13","author":"LM Gockel","year":"2021","journal-title":"ACS Appl Mater Interfaces"},{"key":"pone.0308521.ref060","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.carres.2014.07.020","article-title":"Heparin nanoparticles for \u03b2 amyloid binding and mitigation of \u03b2 amyloid associated cytotoxicity","volume":"405","author":"P Wang","year":"2015","journal-title":"Carbohydrate Research"},{"key":"pone.0308521.ref061","doi-asserted-by":"crossref","first-page":"e22076","DOI":"10.1371\/journal.pone.0022076","article-title":"Heparin Induces Harmless Fibril Formation in Amyloidogenic W7FW14F Apomyoglobin and Amyloid Aggregation in Wild-Type Protein In Vitro.","volume":"6","author":"S Vilasi","year":"2011","journal-title":"PLoS ONE."},{"key":"pone.0308521.ref062","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1073\/pnas.0511256103","article-title":"Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington\u2019s and Parkinson\u2019s diseases.","volume":"103","author":"RA Bodner","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0308521.ref063","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41589-020-0493-1","article-title":"Genetically encoded protein sulfation in mammalian cells","volume":"16","author":"JS Italia","year":"2020","journal-title":"Nat Chem Biol"},{"key":"pone.0308521.ref064","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/j.peptides.2007.08.010","article-title":"Heparin-mimetic sulfated peptides with modulated affinities for heparin-binding peptides and growth factors","volume":"28","author":"SH Kim","year":"2007","journal-title":"Peptides"},{"key":"pone.0308521.ref065","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.tibs.2021.05.003","article-title":"Protein Amyloid Cofactors: Charged Side-Chain Arrays Meet Their Match?","volume":"46","author":"E Lewkowicz","year":"2021","journal-title":"Trends in Biochemical Sciences"},{"key":"pone.0308521.ref066","doi-asserted-by":"crossref","first-page":"e19338","DOI":"10.1371\/journal.pone.0019338","article-title":"Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease.","volume":"6","author":"E Masliah","year":"2011","journal-title":"PLoS ONE."},{"key":"pone.0308521.ref067","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.nbd.2015.04.009","article-title":"Generation and characterization of novel conformation-specific monoclonal antibodies for \u03b1-synuclein pathology","volume":"79","author":"NN Vaikath","year":"2015","journal-title":"Neurobiology of Disease"},{"key":"pone.0308521.ref068","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.str.2022.11.012","article-title":"Benchmarking AlphaFold2 on peptide structure prediction","volume":"31","author":"EF McDonald","year":"2023","journal-title":"Structure"},{"key":"pone.0308521.ref069","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.bpj.2012.01.060","article-title":"Toward a Molecular Understanding of Protein Solubility: Increased Negative Surface Charge Correlates with Increased Solubility","volume":"102","author":"RM Kramer","year":"2012","journal-title":"Biophysical Journal"},{"key":"pone.0308521.ref070","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1021\/mp500533c","article-title":"Specific Ion and Buffer Effects on Protein\u2013Protein Interactions of a Monoclonal Antibody.","volume":"12","author":"D Roberts","year":"2015","journal-title":"Mol Pharmaceutics."},{"key":"pone.0308521.ref071","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12575-017-0060-7","article-title":"Efficient and inexpensive transient expression of multispecific multivalent antibodies in Expi293 cells.","volume":"19","author":"XT Fang","year":"2017","journal-title":"Biol Proced Online"},{"key":"pone.0308521.ref072","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"J Jumper","year":"2021","journal-title":"Nature"},{"key":"pone.0308521.ref073","doi-asserted-by":"crossref","DOI":"10.1101\/2021.10.04.463034","article-title":"Protein complex prediction with AlphaFold-Multimer","author":"R Evans","year":"2021"},{"key":"pone.0308521.ref074","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1093\/nar\/gkg563","article-title":"ExPASy: the proteomics server for in-depth protein knowledge and analysis","volume":"31","author":"E. 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