4.8 Article

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

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 144, Issue 22, Pages 10006-10016

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jacs.2c03232

Keywords

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Funding

  1. Regione Toscana (CERM-TT)
  2. Italian Ministero dell'Istruzione, dell'Universita e della Ricerca [PRIN 2017A2KEPL]
  3. Regione Toscana (BioEnable)
  4. Progetto Dipartimenti di Eccellenza 2018-2022
  5. Recombinant Proteins JOYNLAB laboratory
  6. project FISR2021_SYLCOV
  7. Instruct-ERIC
  8. ESFRI
  9. CERM/CIRMMP Italy center
  10. H2020-INFRAIA iNEXT-Discovery.Structural Biology Research Infrastructures for Translational Research and Discovery [871037]
  11. EOSC-Life Providing an open collaborative space for digital biology in Europe (H2020) [824087]
  12. Glytunes Marie Sklodowska-Curie Action (MSCA) Innovative Training Networks (ITN) H2020MSCA-ITN-2020 [956758]
  13. PANACEA A Pan-European Solid-State NMR Infrastructure for Chemistry-Enabling Access, (H2020) [101008500101008500]
  14. Marie Curie Actions (MSCA) [956758] Funding Source: Marie Curie Actions (MSCA)

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Multispecific biologics are a new class of drugs designed to improve therapeutic efficacy and safety by covalently linking or expressing antibodies and/or proteins as fusion proteins. Solid-state NMR has been used to identify the residue pattern of the programmed cell death ligand 1 (PD-L1) ectodomain involved in interaction with a new multispecific biological drug, as the large size and intrinsic flexibility of complexes are not limiting factors for solid-state NMR.
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-LI) 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.

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