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Population-level analysis of glycoprotein glycoforms

Toledo, Alejandro Gomez LU ; Sorrentino, James T ; Schoffelen, Sanne ; Voldborg, Bjørn ; Velasquez, Erika LU ; Scott, Aaron M LU ; Larson, Göran ; Lewis, Nathan E and Malmström, Johan LU orcid (2026) In mAbs 18(1).
Abstract

The structure and function of many proteins are regulated post-translationally through glycan attachment. These glycans, assembled via competing enzymatic reactions, generate diverse glycoform populations - variants sharing a protein backbone but differing in glycan structures. While current analyses often focus on individual glycoforms, we demonstrate that population-level glycoform analysis - integrating spectral, biosynthetic, and physicochemical relationships - reveals new insights into glycoprotein regulation. Applied to immunoglobulin subclasses and antithrombin III (AT3), this approach provides comprehensive coverage of glycoform repertoires from human and murine plasma and biopharmaceuticals. It also enables sensitive... (More)

The structure and function of many proteins are regulated post-translationally through glycan attachment. These glycans, assembled via competing enzymatic reactions, generate diverse glycoform populations - variants sharing a protein backbone but differing in glycan structures. While current analyses often focus on individual glycoforms, we demonstrate that population-level glycoform analysis - integrating spectral, biosynthetic, and physicochemical relationships - reveals new insights into glycoprotein regulation. Applied to immunoglobulin subclasses and antithrombin III (AT3), this approach provides comprehensive coverage of glycoform repertoires from human and murine plasma and biopharmaceuticals. It also enables sensitive quantification of glycosylation changes arising from in vitro manipulations or in vivo infections. Finally, we introduce a statistical framework adapted from ecological biodiversity studies, revealing that both IgG and AT3 exhibit skewed glycoform distributions shaped by biosynthetic constraints and degradation. Our findings demonstrate the added value of population-level glycoform analysis in understanding protein function and regulation through glycosylation.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glycosylation, Humans, Animals, Mice, Glycoproteins/chemistry, Polysaccharides/chemistry, Immunoglobulin G/chemistry, Antithrombin III/chemistry, Protein Processing, Post-Translational
in
mAbs
volume
18
issue
1
article number
2665879
publisher
Taylor & Francis
external identifiers
  • pmid:42059453
  • scopus:105037562500
ISSN
1942-0862
DOI
10.1080/19420862.2026.2665879
language
English
LU publication?
yes
id
ac073500-41f1-40e0-8471-fe4b971d15ed
date added to LUP
2026-05-07 07:52:05
date last changed
2026-06-05 05:55:57
@article{ac073500-41f1-40e0-8471-fe4b971d15ed,
  abstract     = {{<p>The structure and function of many proteins are regulated post-translationally through glycan attachment. These glycans, assembled via competing enzymatic reactions, generate diverse glycoform populations - variants sharing a protein backbone but differing in glycan structures. While current analyses often focus on individual glycoforms, we demonstrate that population-level glycoform analysis - integrating spectral, biosynthetic, and physicochemical relationships - reveals new insights into glycoprotein regulation. Applied to immunoglobulin subclasses and antithrombin III (AT3), this approach provides comprehensive coverage of glycoform repertoires from human and murine plasma and biopharmaceuticals. It also enables sensitive quantification of glycosylation changes arising from in vitro manipulations or in vivo infections. Finally, we introduce a statistical framework adapted from ecological biodiversity studies, revealing that both IgG and AT3 exhibit skewed glycoform distributions shaped by biosynthetic constraints and degradation. Our findings demonstrate the added value of population-level glycoform analysis in understanding protein function and regulation through glycosylation.</p>}},
  author       = {{Toledo, Alejandro Gomez and Sorrentino, James T and Schoffelen, Sanne and Voldborg, Bjørn and Velasquez, Erika and Scott, Aaron M and Larson, Göran and Lewis, Nathan E and Malmström, Johan}},
  issn         = {{1942-0862}},
  keywords     = {{Glycosylation; Humans; Animals; Mice; Glycoproteins/chemistry; Polysaccharides/chemistry; Immunoglobulin G/chemistry; Antithrombin III/chemistry; Protein Processing, Post-Translational}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Taylor & Francis}},
  series       = {{mAbs}},
  title        = {{Population-level analysis of glycoprotein glycoforms}},
  url          = {{http://dx.doi.org/10.1080/19420862.2026.2665879}},
  doi          = {{10.1080/19420862.2026.2665879}},
  volume       = {{18}},
  year         = {{2026}},
}