Native Top-Down Mass Spectrometry Reveals a Role for Interfacial Glycans on Therapeutic Cytokine and Hormone Assemblies.
Angew Chem Weinheim Bergstr Ger
; 134(49): e202213170, 2022 Dec 05.
Article
en En
| MEDLINE
| ID: mdl-38504999
ABSTRACT
Oligomerization and glycosylation modulate therapeutic glycoprotein stability and efficacy. The interplay between these two critical attributes on therapeutic glycoproteins, is however often hard to define. Here, we present a native top-down mass spectrometry (MS) approach to assess the glycosylation status of therapeutic cytokine and hormone assemblies and relate interfacial glycan occupancy to complex stability. We found that interfacial O-glycan stabilizes tumor necrosis factor-α trimer. On the contrary, interferon-ß1a dimerization is independent of glycosylation. Moreover, we discovered a unique distribution of N-glycans on the follicle-stimulating hormone α subunit. We found that the interfacial N-glycan, at Asn52 of the α subunit, interacts extensively with the ß subunit to regulate the dimer assembly. Overall, we have exemplified a method to link glycosylation with assembly status, for cytokines and hormones, critical for informing optimal stability and bioavailability.
Texto completo:
1
Colección:
01-internacional
Idioma:
En
Revista:
Angew Chem Weinheim Bergstr Ger
/
Angew. chem. (Weinheim Bergdtr. Germ.)
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Angewandte chemie (Weinheim an der Bergstrasse, Germany)
Asunto de la revista:
BIOFISICA
/
QUIMICA
Año:
2022
Tipo del documento:
Article