{"entity": "publication", "iuid": "1dd1188ac1a943fdbab88493f55de04e", "timestamp": "2026-09-25T23:04:35.437Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1dd1188ac1a943fdbab88493f55de04e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1dd1188ac1a943fdbab88493f55de04e"}}, "title": "A charged tail on anti-\u03b1-Synuclein antibodies does not enhance their affinity to \u03b1-Synuclein fibrils.", "authors": [{"family": "Petersen", "given": "Inga", "initials": "I"}, {"family": "Godec", "given": "Ana", "initials": "A"}, {"family": "Ranjbarian", "given": "Farahnaz", "initials": "F"}, {"family": "Hofer", "given": "Anders", "initials": "A", "orcid": "0000-0003-2890-2957", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5bbee58211d431689b885b975f9ebae.json"}}, {"family": "Mirabello", "given": "Claudio", "initials": "C"}, {"family": "Hultqvist", "given": "Greta", "initials": "G", "orcid": "0000-0002-4136-6792", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7ed4198fd7ef45d98cc951c871d0ba17.json"}}], "type": "journal article", "published": "2024-08-29", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "19", "issue": "8", "pages": "e0308521", "issn-l": "1932-6203"}, "abstract": "The aggregation of \u03b1-Synuclein (\u03b1Syn) is strongly linked to neuronal death in Parkinson's disease and other synucleinopathies. 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's 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' 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' binding to \u03b1Syn aggregates. Fine-tuning the design of the peptide tail to avoid its interaction with the antibodies' CDR and to better mimic relevant characteristics of heparan sulphates for \u03b1Syn aggregate binding may help overcome the limitations observed in this study.", "doi": "10.1371/journal.pone.0308521", "pmid": "39208301", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11361660"}, {"db": "pii", "key": "PONE-D-24-20655"}], "notes": [], "created": "2026-09-23T15:40:47.864Z", "modified": "2026-09-23T15:40:47.965Z"}