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-β1a 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 β 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.
CITATION STYLE
Wu, D., & Robinson, C. V. (2022). Native Top-Down Mass Spectrometry Reveals a Role for Interfacial Glycans on Therapeutic Cytokine and Hormone Assemblies. Angewandte Chemie - International Edition, 61(49). https://doi.org/10.1002/anie.202213170
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