{"entity": "publication", "iuid": "5a3d2a140dcc4278a68afc3ab6fa0653", "timestamp": "2026-08-26T22:58:23.104Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5a3d2a140dcc4278a68afc3ab6fa0653.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5a3d2a140dcc4278a68afc3ab6fa0653"}}, "title": "Structural and antigen-binding surface definition of an anti-CD93 monoclonal antibody for the treatment of degenerative vascular eye diseases.", "authors": [{"family": "Raucci", "given": "Luisa", "initials": "L"}, {"family": "Perrone", "given": "Cosimo Damiano", "initials": "CD"}, {"family": "Barbera", "given": "Stefano", "initials": "S"}, {"family": "de Boer", "given": "Laurens Julius", "initials": "LJ"}, {"family": "Tosi", "given": "Gian Marco", "initials": "GM"}, {"family": "Brunetti", "given": "Jlenia", "initials": "J"}, {"family": "Bracci", "given": "Luisa", "initials": "L"}, {"family": "Pozzi", "given": "Cecilia", "initials": "C"}, {"family": "Galvagni", "given": "Federico", "initials": "F"}, {"family": "Orlandini", "given": "Maurizio", "initials": "M"}], "type": "journal article", "published": "2025-05-00", "journal": {"title": "Int J Biol Macromol", "issn": "1879-0003", "volume": "309", "issue": "Pt 4", "pages": "143118", "issn-l": null}, "abstract": "CD93 is a receptor predominantly expressed on the surface of endothelial cells, where it plays a pivotal role in angiogenesis through its interaction with the extracellular matrix. In our previous studies, we identified the monoclonal antibody 4E1 as a potent inhibitor of angiogenesis by targeting the CD93-Multimerin-2 axis. Here, we report the development of 4E1 as a recombinant whole immunoglobulin and a single-chain variable fragment, designated sc-4E. Both formats retained the binding properties of the parental monoclonal antibody and exhibited comparable inhibitory effects on endothelial cell migration and differentiation. To elucidate the molecular basis of the 4E1-CD93 interaction, we initially employed machine learning-based modeling and docking analyses of the variable heavy and light domains of 4E1. Subsequent crystallographic analysis of sc-4E provided high-resolution structural insights, confirming and validating the predicted model. Further docking experiments and molecular dynamics simulations using the crystallographic structures of CD93 and sc-4E revealed that the interaction is primarily mediated by the CDR-H3 and CDR-L2 loops. Notably, these regions engage with the sushi-like domain of CD93, which is critical for its interaction with Multimerin-2. This comprehensive structural and functional characterization of 4E1 and sc-4E underscores their potential as anti-angiogenic agents. By effectively inhibiting endothelial cell migration and differentiation, 4E1 derivatives represent promising therapeutic candidates for the treatment of ocular vascular diseases driven by pathological angiogenesis.", "doi": "10.1016/j.ijbiomac.2025.143118", "pmid": "40228767", "labels": [], "xrefs": [{"db": "pii", "key": "S0141-8130(25)03670-0"}], "notes": [], "created": "2026-08-21T11:20:34.015Z", "modified": "2026-08-21T11:20:34.030Z"}