HDX-MS study on garadacimab binding to activated FXII reveals potential binding interfaces through differential solvent exposure
| Autor: | Saw Yen Ow, Eugene A. Kapp, Vesna Tomasetig, Anton Zalewski, Jason Simmonds, Con Panousis, Michael J. Wilson, Andrew D. Nash, Matthias Pelzing |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | mAbs, Vol 15, Iss 1 (2023) |
| Druh dokumentu: | article |
| ISSN: | 19420862 1942-0870 1942-0862 |
| DOI: | 10.1080/19420862.2022.2163459 |
| Popis: | ABSTRACTHageman factor (FXII) is an essential component in the intrinsic coagulation cascade and a therapeutic target for the prophylactic treatment of hereditary angioedema (HAE). CSL312 (garadacimab) is a novel high-affinity human antibody capable of blocking activated FXII activity that is currently undergoing Phase 3 clinical trials in HAE. Structural studies using hydrogen/deuterium exchange coupled to mass spectrometry revealed evidence of interaction between the antibody and regions surrounding the S1 specificity pocket of FXII, including the 99-loop, 140-loop, 180-loop, and neighboring regions. We propose complementarity-determining regions (CDRs) in heavy-chain CDR2 and CDR3 as potential paratopes on garadacimab, and the 99-loop, 140-loop, 180-loop, and 220-loop as binding sites on the beta chain of activated FXII (β-FXIIa). |
| Databáze: | Directory of Open Access Journals |
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