Evidence map›Paper›PMID 25054442›Full record

ArticleMolecules (Basel, Switzerland)2014

A combinatorial approach to biophysically characterise chemokine-glycan binding affinities for drug development.

Tanja Gerlza, Bianca Hecher, Dalibor Jeremic, Thomas Fuchs, Martha Gschwandtner, Angelika Falsone, Bernd Gesslbauer, Andreas J Kungl

Abstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–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

21 citing papers in PubMed.

  1. Review
  2. Article
  3. Antiviral Activity ofPathogens (Basel, Switzerland) · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. The Role of Heparan Sulfate in CCL26-Induced Eosinophil Chemotaxis.International journal of molecular sciences · 2022
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Glycosaminoglycanomics: where we are.Glycoconjugate journal · 2017
    Review
  18. Article
  19. Article
  20. 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

8 authors.

Tanja GerlzaInstitute of Pharmaceutical Sciences, Karl-Franzens-University Graz, Humboldtstrasse 46, A-8010 Graz, Austria.
Bianca HecherInstitute of Pharmaceutical Sciences, Karl-Franzens-University Graz, Humboldtstrasse 46, A-8010 Graz, Austria.
Dalibor JeremicProtAffin Biotechnologie AG, Reininghausstrasse 13a, A-802 Graz, Austria.
Thomas FuchsProtAffin Biotechnologie AG, Reininghausstrasse 13a, A-802 Graz, Austria.
Martha GschwandtnerProtAffin Biotechnologie AG, Reininghausstrasse 13a, A-802 Graz, Austria.
Angelika FalsoneProtAffin Biotechnologie AG, Reininghausstrasse 13a, A-802 Graz, Austria.
Bernd GesslbauerInstitute of Pharmaceutical Sciences, Karl-Franzens-University Graz, Humboldtstrasse 46, A-8010 Graz, Austria.
Andreas J KunglInstitute of Pharmaceutical Sciences, Karl-Franzens-University Graz, Humboldtstrasse 46, A-8010 Graz, Austria. andreas.kungl@uni-graz.at.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemokine binding to glycosaminoglycans (GAGs) is recognised to be an important step in inflammation and other pathological disorders like tumor growth and metastasis. Although different ways and strategies to interfere with these interactions are being pursued, no major breakthrough in the development of glycan-targeting drugs has been reported so far. We have engineered CXCL8 towards a dominant-negative form of this chemokine (dnCXCL8) which was shown to be highly active in various inflammatory animal models due to its inability to bind/activate the cognate CXCL8 GPC receptors on neutrophils in combination with its significantly increased GAG-binding affinity [1]. For the development of GAG-targeting chemokine-based biopharmaceuticals, we have established a repertoire of methods which allow the quantification of protein-GAG interactions. Isothermal fluorescence titration (IFT), surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and a novel ELISA-like competition assay (ELICO) have been used to determine Kd and IC50 values for CXCL8 and dnCXCL8 interacting with heparin and heparan sulfate (HS), the proto-typical members of the GAG family. Although the different methods gave different absolute affinities for the four protein-ligand pairs, the relative increase in GAG-binding affinity of dnCXCL8 compared to the wild type chemokine was found by all methods. In combination, these biophysical methods allow to discriminate between unspecific and specific protein-GAG interactions.

Indexed as

Drug DesignAnimalsAnti-Inflammatory AgentsCell LineGlycosaminoglycansHumansInflammationInterleukin-8Protein BindingProtein EngineeringReceptors, CXCRAnti-Inflammatory AgentsCXCL8 protein, humanGlycosaminoglycansInterleukin-8Receptors, CXCR

Identifiers

PMID25054442
PMCPMC6271861

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Registered trials

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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.