Evidence map›Paper›PMID 38339208›Full record

ArticleInternational journal of molecular sciences2024

Tyrosine Sulfation at Antibody Light Chain CDR-1 Increases Binding Affinity and Neutralization Potency to Interleukine-4.

Aaron M D'Antona, Julie M Lee, Melvin Zhang, Clarence Friedman, Tao He, Lidia Mosyak, Eric Bennett, Laura Lin, Maddison Silverman, Funi Cometa and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 1 institution in 1 country.

Aaron M D'AntonaBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Julie M LeeTranslational Clinical Sciences, Pfizer Discovery & Early Development, 610 Main Street, Cambridge, MA 02139, USA.
Melvin ZhangInflammation and Immunology Research Unit, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Clarence FriedmanBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Tao HeBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Lidia MosyakBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Eric BennettBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Laura LinBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Maddison SilvermanBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Funi CometaBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Caryl MeadeBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Tyler HagemanBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.ORCID 0000-0003-0112-8893
Eric SousaBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Justin CohenBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Kimberly MarquetteBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Darren FergusonBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Xiaotian ZhongBioMedicine Design, Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
Pfizer (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Structure and function of therapeutic antibodies can be modulated by a variety of post-translational modifications (PTM). Tyrosine (Tyr) sulfation is a type of negatively charged PTM that occurs during protein trafficking through the Golgi. In this study, we discovered that an anti-interleukin (IL)-4 human IgG1, produced by transiently transfected HEK293 cells, contained a fraction of unusual negatively charged species. Interestingly, the isolated acidic species exhibited a two-fold higher affinity to IL-4 and a nearly four-fold higher potency compared to the main species. Mass spectrometry (MS) showed the isolated acidic species possessed an +80-Dalton from the expected mass, suggesting an occurrence of Tyr sulfation. Consistent with this hypothesis, we show the ability to control the acidic species during transient expression with the addition of Tyr sulfation inhibitor sodium chlorate or, conversely, enriched the acidic species from 30% to 92% of the total antibody protein when the IL-4 IgG was co-transfected with tyrosylprotein sulfotransferase genes. Further MS and mutagenesis analysis identified a Tyr residue at the light chain complementarity-determining region-1 (CDRL-1), which was sulfated specifically. These results together have demonstrated for the first time that Tyr sulfation at CDRL-1 could modulate antibody binding affinity and potency to a human immune cytokine.

Indexed as

Interleukin-4TyrosineGolgi ApparatusHEK293 CellsHumansMutagenesisInterleukin-4Tyrosineantigen-binding affinitycomplementarity-determining region (CDR)cytokine signalinginterleukine-4tyrosine sulfation

Identifiers

PMID38339208
PMCPMC10855961
OpenAlexW4391540859

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.