Determination of the Rituximab Binding Site to the CD20 Epitope Using SPOT Synthesis and Surface Plasmon Resonance Analyses
| Autor: | Francisco Santos-Schneider, Mathieu Galibert, Christophe Nguyen, Rémy Lartia, Didier Boturyn, Gudrun Aldrian, Jérôme Dejeu, Liliane Coche-Guérente, Franck Molina, Laure Bar |
|---|---|
| Přispěvatelé: | Département de Chimie Moléculaire (DCM), Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Sys2Diag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (Sys2Diag), Centre National de la Recherche Scientifique (CNRS)-Alcediag |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.drug_class
Chronic lymphocytic leukemia Computational biology 010402 general chemistry Monoclonal antibody 01 natural sciences Epitope Analytical Chemistry Antibodies Monoclonal Murine-Derived Epitopes [CHIM.ANAL]Chemical Sciences/Analytical chemistry hemic and lymphatic diseases medicine Surface plasmon resonance ComputingMilieux_MISCELLANEOUS CD20 Binding Sites biology Chemistry 010401 analytical chemistry Surface Plasmon Resonance medicine.disease Antigens CD20 3. Good health 0104 chemical sciences biology.protein Paratope Rituximab Antibody medicine.drug |
| Zdroj: | Analytical Chemistry Analytical Chemistry, American Chemical Society, In press, 93 (17), pp.6865-6872. ⟨10.1021/acs.analchem.1c00960⟩ |
| ISSN: | 0003-2700 1520-6882 |
| Popis: | Antibodies not only play a major role in clinical diagnostics and biopharmaceutical analysis but also are a class of drugs that are regularly used to treat numerous diseases. The identification of antibody-epitope binding sites is then of great interest to many emerging medical and bioanalytical applications, particularly to design monoclonal antibodies (mAb) mimics taking advantage of amino acid residues involved in the binding. Among relevant antibodies, the monoclonal antibody rituximab has received significant attention as it is exploited to treat several cancers including non-Hodgkin's lymphoma and chronic lymphocytic leukemia, as well as some autoimmune disorders such as rheumatoid arthritis. The binding of rituximab to the targeted cells occurs via the recognition of the CD20 epitope. A crystallographic study has shown that the binding area, named paratope, is located at the surface of rituximab. Combining the SPOT method and the complementary surface plasmon resonance technique allowed us to detect an extended recognition domain buried in the pocket of the rituximab Fab formed by four β-sheets. More generally, the present study offers a comprehensive approach to identify antibody-epitope binding sites. |
| Databáze: | OpenAIRE |
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