Epitope Mapping and Binding Assessment by Solid-State NMR Provide a Way for the Development of Biologics under the Quality by Design Paradigm

Autor: Domenico Rizzo, Linda Cerofolini, Stefano Giuntini, Luisa Iozzino, Carlo Pergola, Francesca Sacco, Angelo Palmese, Enrico Ravera, Claudio Luchinat, Fabio Baroni, Marco Fragai
Rok vydání: 2022
Předmět:
Zdroj: Journal of the American Chemical Society
ISSN: 1520-5126
0002-7863
DOI: 10.1021/jacs.2c03232
Popis: Multispecific biologics are an emerging class of drugs, in which antibodies and/or proteins designed to bind pharmacological targets are covalently linked or expressed as fusion proteins to increase both therapeutic efficacy and safety. Epitope mapping on the target proteins provides key information to improve the affinity and also to monitor the manufacturing process and drug stability. Solid-state NMR has been here used to identify the pattern of the residues of the programmed cell death ligand 1 (PD-L1) ectodomain that are involved in the interaction with a new multispecific biological drug. This is possible because the large size and the intrinsic flexibility of the complexes are not limiting factors for solid-state NMR.
Databáze: OpenAIRE