Evidence map›Paper›PMID 26824070›Full record

ArticleScience advances2016

Chemical synthesis of erythropoietin glycoforms for insights into the relationship between glycosylation pattern and bioactivity.

Masumi Murakami, Tatsuto Kiuchi, Mika Nishihara, Katsunari Tezuka, Ryo Okamoto, Masayuki Izumi, Yasuhiro Kajihara

Abstract read
In one paragraph

Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

41 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018
    Pooled it
  2. Article
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  4. Revealing the Biological Effect of theJournal of the American Chemical Society · 2026
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  8. Unveiling the Accurate Site-SpecificAnalytical chemistry · 2025
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  14. D-Peptide and D-Protein Technology: Recent Advances, Challenges, and Opportunities.Chembiochem : a European journal of chemical biology · 2023
    Review
  15. Total synthesis of interleukin-2Chemical science · 2023
    Article
  16. Article
  17. Chemical and Enzymatic Synthesis of Sialylated Glycoforms of Human Erythropoietin.Angewandte Chemie (International ed. in English) · 2021
    Article
  18. Article
  19. Recent Advances in the Chemical Biology ofMolecules (Basel, Switzerland) · 2021
    Review
  20. Review
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

7 authors.

Masumi MurakamiDepartment of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka 5460-0043, Japan.
Tatsuto KiuchiDepartment of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka 5460-0043, Japan.
Mika NishiharaGlytech Inc., 134, Chudoji, Minamimachi KRP#1-109, Shimogyo-ku, Kyoto 600-8813, Japan.
Katsunari TezukaGlytech Inc., 134, Chudoji, Minamimachi KRP#1-109, Shimogyo-ku, Kyoto 600-8813, Japan.
Ryo OkamotoDepartment of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka 5460-0043, Japan.
Masayuki IzumiDepartment of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka 5460-0043, Japan.ORCID 0000-0001-6486-9678
Yasuhiro KajiharaDepartment of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka 5460-0043, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The role of sialyloligosaccharides on the surface of secreted glycoproteins is still unclear because of the difficulty in the preparation of sialylglycoproteins in a homogeneous form. We selected erythropoietin (EPO) as a target molecule and designed an efficient synthetic strategy for the chemical synthesis of a homogeneous form of five EPO glycoforms varying in glycosylation position and the number of human-type biantennary sialyloligosaccharides. A segment coupling strategy performed by native chemical ligation using six peptide segments including glycopeptides yielded homogeneous EPO glycopeptides, and folding experiments of these glycopeptides afforded the correctly folded EPO glycoforms. In an in vivo erythropoiesis assay in mice, all of the EPO glycoforms displayed biological activity, in particular the EPO bearing three sialyloligosaccharides, which exhibited the highest activity. Furthermore, we observed that the hydrophilicity and biological activity of the EPO glycoforms varied depending on the glycosylation pattern. This knowledge will pave the way for the development of homogeneous biologics by chemical synthesis.

Indexed as

Amino Acid SequenceAnimalsCell LineErythropoietinGlycopeptidesGlycosylationHumansMiceMice, Inbred BALB COligosaccharidesErythropoietinGlycopeptidesOligosaccharidessialooligosaccharidesBiotechnologychemical glycoprotein synthesischemical protein synthesisglycoproteinglycosylationoligosaccharide

Identifiers

PMID26824070
PMCPMC4730857

What OpenQuestion holds

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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.