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mimotope peptide modified pompon mum-like magnetic microparticles for precise recognition,capture and biotransformation analysis of rituximab in biological fluids

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1317-1328页

作者： Jiawen Yang Aixuan Zhou Minyi Li Qiaoxian He Jingwei Zhou Jacques Crommen Wentao Wang Zhengjin Jiang Qiqin Wang Institute of Pharmaceutical Analysis College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of ChinaJinan UniversityGuangzhou 510632China Laboratory for the Analysis of Medicines Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium SCIEX Shanghai 200050China

Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge *** this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first *** from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported *** the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum *** also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient ***,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful ***,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.

关键词： Therapeutic monoclonal antibody mimotope peptide Precise recognition peptide-based biomaterials Biotransformation Patient serum

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