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
ISSN: 1520-5126
Titre abrégé: J Am Chem Soc
Pays: United States
ID NLM: 7503056

Informations de publication

Date de publication:
08 06 2022
Historique:
pubmed: 27 5 2022
medline: 10 6 2022
entrez: 26 5 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35617699
doi: 10.1021/jacs.2c03232
pmc: PMC9185746
doi:

Substances chimiques

Antibodies 0
Biological Products 0
Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

10006-10016

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Auteurs

Domenico Rizzo (D)

Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.

Linda Cerofolini (L)

Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.

Stefano Giuntini (S)

Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.

Luisa Iozzino (L)

Analytical Development Biotech Department, Merck Serono S.p.a, Via Luigi Einaudi, 11, 00012 Guidonia, RM, Italy.

Carlo Pergola (C)

Analytical Development Biotech Department, Merck Serono S.p.a, Via Luigi Einaudi, 11, 00012 Guidonia, RM, Italy.

Francesca Sacco (F)

Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Analytical Development Biotech Department, Merck Serono S.p.a, Via Luigi Einaudi, 11, 00012 Guidonia, RM, Italy.

Angelo Palmese (A)

Analytical Development Biotech Department, Merck Serono S.p.a, Via Luigi Einaudi, 11, 00012 Guidonia, RM, Italy.

Enrico Ravera (E)

Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.

Claudio Luchinat (C)

Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.

Fabio Baroni (F)

Analytical Development Biotech Department, Merck Serono S.p.a, Via Luigi Einaudi, 11, 00012 Guidonia, RM, Italy.

Marco Fragai (M)

Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.

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Classifications MeSH