The Impact of Immunoglobulin G1 Fc Sialylation on Backbone Amide H/D Exchange.
Fc glycosylation
FcγR binding
antibody conformation
antibody effector function
biopharmaceutical
higher-order structure
hydrogen/deuterium exchange
mass spectrometry
sialic acid linkage
structure-function
Journal
Antibodies (Basel, Switzerland)
ISSN: 2073-4468
Titre abrégé: Antibodies (Basel)
Pays: Switzerland
ID NLM: 101587489
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
30
08
2019
revised:
24
09
2019
accepted:
26
09
2019
entrez:
5
10
2019
pubmed:
5
10
2019
medline:
5
10
2019
Statut:
epublish
Résumé
The usefulness of higher-order structural information provided by hydrogen/deuterium exchange-mass spectrometry (H/DX-MS) for the structural impact analyses of chemical and post-translational antibody modifications has been demonstrated in various studies. However, the structure-function assessment for protein drugs in biopharmaceutical research and development is often impeded by the relatively low-abundance (below 5%) of critical quality attributes or by overlapping effects of modifications, such as glycosylation, with chemical amino acid modifications; e.g., oxidation or deamidation. We present results demonstrating the applicability of the H/DX-MS technique to monitor conformational changes of specific Fc glycosylation variants produced by in vitro glyco-engineering technology. A trend towards less H/DX in Fc Cγ2 domain segments correlating with larger glycan structures could be confirmed. Furthermore, significant deuterium uptake differences and corresponding binding properties to Fc receptors (as monitored by SPR) between α-2,3- and α-2,6-sialylated Fc glycosylation variants were verified at sensitive levels.
Identifiants
pubmed: 31581521
pii: antib8040049
doi: 10.3390/antib8040049
pmc: PMC6963987
pii:
doi:
Types de publication
Journal Article
Langues
eng
Déclaration de conflit d'intérêts
F.K., L.B., S.M., M.T., H.W., D.R. and P.B. are employees of Roche Diagnostics GmbH; C.A., F.C. and H.W. are employees of F. Hoffmann-La Roche Ltd. The authors declare no conflict of interest.
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