Evidence map›Paper›PMID 35216161›Full record

ArticleInternational journal of molecular sciences2022

Structure-Based Cyclic Glycoprotein Ibα-Derived Peptides Interfering with von Willebrand Factor-Binding, Affecting Platelet Aggregation under Shear.

Johana Hrdinova, Delia I Fernández, Bogac Ercig, Bibian M E Tullemans, Dennis P L Suylen, Stijn M Agten, Kerstin Jurk, Tilman M Hackeng, Karen Vanhoorelbeke, Jan Voorberg and 4 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Biomedicines · 2025
    Article
  2. Structural bioinformatics for rational drug design.Research and practice in thrombosis and haemostasis · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. The IRAK-M death domain: a tale of three surfaces.Frontiers in molecular biosciences · 2023
    Article
  8. Article
  9. Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022
    Review
  10. Article
  11. Molecular Mechanisms of Hemostasis, Thrombosis and Thrombo-Inflammation.International journal of molecular sciences · 2022
    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

14 authors at 5 institutions in 4 countries.

Johana HrdinovaDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0001-6095-8972
Delia I FernándezDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-5055-9019
Bogac ErcigDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
Bibian M E TullemansDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
Dennis P L SuylenDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
Stijn M AgtenDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-5973-272X
Kerstin JurkCenter for Thrombosis and Hemostasis (CTH), University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.ORCID 0000-0001-5313-4035
Tilman M HackengDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0003-0142-0843
Karen VanhoorelbekeLaboratory for Thrombosis Research, Interdisciplinary Research Facility Life Sciences, Katholieke Universiteit Leuven Campus Kulak Kortrijk, 8500 Kortrijk, Belgium.
Jan VoorbergDepartment of Molecular and Cellular Hemostasis, Sanquin-Academic Medical Center, 1011 LZ Amsterdam, The Netherlands.
Chris P M ReutelingspergerDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-2334-9403
Kanin WichapongDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-9678-7084
Johan W M HeemskerkDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-2848-5121
Gerry A F NicolaesDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
Maastricht University · NLAmsterdam UMC Location University of Amsterdam · NLJohannes Gutenberg University Mainz · DEKU Leuven · BEUniversidade de Santiago de Compostela · ES

Funding

European Union 675746European Union 766118
6 · The paper itself

Abstract

The plasmatic von Willebrand factor (VWF) circulates in a compact form unable to bind platelets. Upon shear stress, the VWF A1 domain is exposed, allowing VWF-binding to platelet glycoprotein Ib-V-IX (GPIbα chain). For a better understanding of the role of this interaction in cardiovascular disease, molecules are needed to specifically interfere with the opened VWF A1 domain interaction with GPIbα. Therefore, we in silico designed and chemically synthetized stable cyclic peptides interfering with the platelet-binding of the VWF A1 domain per se or complexed with botrocetin. Selected peptides (26-34 amino acids) with the lowest-binding free energy were: the monocyclic mono- vOn Willebrand factoR-GPIbα InTerference (ORbIT) peptide and bicyclic bi-ORbIT peptide. Interference of the peptides in the binding of VWF to GPIb-V-IX interaction was retained by flow cytometry in comparison with the blocking of anti-VWF A1 domain antibody CLB-RAg35. In collagen and VWF-dependent whole-blood thrombus formation at a high shear rate, CLB-RAg35 suppressed stable platelet adhesion as well as the formation of multilayered thrombi. Both peptides phenotypically mimicked these changes, although they were less potent than CLB-RAg35. The second-round generation of an improved peptide, namely opt-mono-ORbIT (28 amino acids), showed an increased inhibitory activity under flow. Accordingly, our structure-based design of peptides resulted in physiologically effective peptide-based inhibitors, even for convoluted complexes such as GPIbα-VWF A1.

Indexed as

Platelet AggregationAnimalsBinding SitesBlood PlateletsCells, CulturedHorsesHumansMicrofluidicsPeptidesPlatelet Glycoprotein GPIb-IX ComplexProtein BindingStress, Mechanicalvon Willebrand FactorPeptidesPlatelet Glycoprotein GPIb-IX Complexvon Willebrand Factorglycoprotein Ibin silico peptide designplateletsthrombusvon Willebrand factor

Identifiers

PMID35216161
PMCPMC8876638
OpenAlexW4212935099

What Socratic holds

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LicenceCC BY
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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 Socratic graph.