Evidence map›Paper›PMID 32471866›Full record

ArticleThe Journal of biological chemistry2020

Engineered anti-inflammatory peptides inspired by mapping an evasin-chemokine interaction.

Benoit Darlot, James R O Eaton, Lucia Geis-Asteggiante, Gopala K Yakala, Kalimuthu Karuppanan, Graham Davies, Carol V Robinson, Akane Kawamura, Shoumo Bhattacharya

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. 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
0.7field-weighted citation impact, top 29% 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, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133Arteriosclerosis, thrombosis, and vascular biology · 2024
    Article
  6. Article
  7. Review
  8. Article
  9. Immunomodulatory Proteins in Tick Saliva From a Structural Perspective.Frontiers in cellular and infection microbiology · 2021
    Review
  10. Article
  11. 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

9 authors at 1 institution in 1 country.

Benoit DarlotChemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-3679-4071
James R O EatonChemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.
Lucia Geis-AsteggianteChemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.
Gopala K YakalaDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
Kalimuthu KaruppananDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
Graham DaviesDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-9134-9088
Carol V RobinsonChemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.
Akane KawamuraChemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom akane.kawamura@ncl.ac.uk sbhattac@well.ox.ac.uk.
Shoumo BhattacharyaDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom akane.kawamura@ncl.ac.uk sbhattac@well.ox.ac.uk.ORCID 0000-0002-5571-0478
University of Oxford · GB

Funding

British Heart Foundation CH/09/003/26631British Heart Foundation PG/16/100/32632British Heart Foundation RE/13/1/30181British Heart Foundation RG/18/1/33351Medical Research Council MR/N020413/1
6 · The paper itself

Abstract

Chemokines mediate leukocyte migration and homeostasis and are key targets in inflammatory diseases including atherosclerosis, cytokine storm, and chronic autoimmune disease. Chemokine redundancy and ensuing network robustness has frustrated therapeutic development. Salivary evasins from ticks bind multiple chemokines to overcome redundancy and are effective in several preclinical disease models. Their clinical development has not progressed because of concerns regarding potential immunogenicity, parenteral delivery, and cost. Peptides mimicking protein activity can overcome the perceived limitations of therapeutic proteins. Here we show that peptides possessing multiple chemokine-binding and anti-inflammatory activities can be developed from the chemokine-binding site of an evasin. We used hydrogen-deuterium exchange MS to map the binding interface of the evasin P672 that physically interacts with C-C motif chemokine ligand (CCL) 8 and synthesized a 16-mer peptide (BK1.1) based on this interface region in evasin P672. Fluorescent polarization and native MS approaches showed that BK1.1 binds CCL8, CCL7, and CCL18 and disrupts CCL8 homodimerization. We show that a BK1.1 derivative, BK1.3, has substantially improved ability to disrupt P672 binding to CCL8, CCL2, and CCL3 in an AlphaScreen assay. Using isothermal titration calorimetry, we show that BK1.3 directly binds CCL8. BK1.3 also has substantially improved ability to inhibit CCL8, CCL7, CCL2, and CCL3 chemotactic function

Indexed as

Protein EngineeringAmino Acid SequenceAnimalsAnti-Inflammatory AgentsChemokine CCL8DimerizationHumansMass SpectrometryPeptidesProtein BindingReceptors, ChemokineSequence Homology, Amino AcidTicksAnti-Inflammatory AgentsCCL8 protein, humanChemokine CCL8PeptidesReceptors, ChemokineC–C motif chemokine ligand (CCL)chemokinechemotaxisevasinhost–pathogen interactionhydrogen exchange mass spectrometryimmune responseinflammationinnate immunitymass spectrometrypeptide interactionpeptidesprotein–protein interactionprotein structuretick

Identifiers

PMID32471866
PMCPMC7415964
OpenAlexW3031741277

What OpenQuestion holds

Textmetadata
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.