Detecting features of antibody structure through their mediator-accessible redox activities.

Autor:	Motabar D; Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, USA., Kim E; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, USA., Li J; Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, USA., Zhao Z; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, USA., Mouchahoir T; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; National Institute of Standards and Technology, Gaithersburg, MD, USA., Gallagher DT; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; National Institute of Standards and Technology, Gaithersburg, MD, USA., Schiel JE; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; National Institute of Standards and Technology, Gaithersburg, MD, USA., Garige M; Laboratory of Molecular Oncology, Division of Biotechnology Review and Research-I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD, USA., Sourbier C; Laboratory of Molecular Oncology, Division of Biotechnology Review and Research-I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD, USA., Payne GF; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA. gpayne@umd.edu.; Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, USA. gpayne@umd.edu., Bentley WE; Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA. bentley@umd.edu.; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA. bentley@umd.edu.; Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, USA. bentley@umd.edu.
Jazyk:	angličtina
Zdroj:	Nature chemical biology [Nat Chem Biol] 2024 Dec 02. Date of Electronic Publication: 2024 Dec 02.
DOI:	10.1038/s41589-024-01778-z
Abstrakt:	Protein function relies on sequence, folding and post-translational modification and molecular measurements are commonly used to reveal these structural features. Here, we report an alternative approach that represents these molecular features as readily measurable electronic patterns and validate this experimental approach by detecting structural perturbations commonly encountered during protein biomanufacturing. We studied a monoclonal antibody standard (from the National Institute of Standards and Technology) and focused on the electronic detection of variants that have undergone interchain disulfide bond reduction and methionine oxidation. Electronic detection of these structural perturbations is based on mediated electrochemical probing (MEP) that discerns patterns associated with the antibody's mediator-accessible redox activity. We demonstrate that MEP can rapidly (within minutes) and quantitatively detect alterations in the antibody's structural features and produce robust electronic signals that could enable monitoring of biomanufacturing processes. The ability to transduce information regarding a protein's structural perturbations into a more convenient electronic domain offers opportunities to apply the power of microelectronics and real-time data analytics to chemical and biological analysis. Competing Interests: Competing interests: The authors declare no competing interests. (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze:	MEDLINE
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