Evidence map›Paper›PMID 40272315›Full record

ArticleAngewandte Chemie (International ed. in English)2025

Macrocyclic Peptide Probes for Immunomodulatory Protein CD59: Potent Modulators of Bacterial Toxin Activity and Antibody-Dependent Cytotoxicity.

Jasmine K Bickel, Ammar I S Ahmed, Aidan B Pidd, Rhodri M Morgan, Tom E McAllister, Sam Horrell, Emma C Couves, Hemavathi Nagaraj, Edward J Bartlett, Kamel El Omari and 3 more

Erratum issuedAbstract read
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In one paragraph

Article in Angewandte Chemie (International ed. in English), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Jasmine K Bickel *Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, W12 0BZ, UK.
Ammar I S Ahmed *Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, W12 0BZ, UK.
Aidan B PiddDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, W12 0BZ, UK.
Rhodri M MorganDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.
Tom E McAllisterChemistry-School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, Newcastle, NE1 7RU, UK.
Sam HorrellDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.
Emma C CouvesDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.
Hemavathi NagarajThe Francis Crick Institute, London, NW1 1AT, UK.
Edward J BartlettDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, W12 0BZ, UK.
Kamel El OmariDiamond Light Source, Harwell Science & Innovation Campus, Didcot, Oxford, OX11 0DE, UK.
Akane KawamuraChemistry-School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, Newcastle, NE1 7RU, UK.
Doryen BubeckDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.
Edward W TateDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, W12 0BZ, UK.

Funding

Cancer Research UK Convergence Science Centre at Imperial College London C24523/A26234CRUK C29637/A20183CRUK DRCNPGNov21\100001Engineering and Physical Sciences Research Council EP/L015498/1EPSRC Impact Acceleration Account EP/R511547/1European Research Council 101003111European Research Council 864751Islamic Development BankNIHR Imperial Biomedical Research Centre RDF01
6 · The paper itself

Abstract

CD59 is an immunomodulatory cell surface receptor associated with human disease. Despite its importance in complement regulation and bacterial pathogenesis, CD59 remains a challenging therapeutic target. Research to date has focused on antibody or protein-based strategies. Here we present a new approach to target CD59 using macrocyclic peptides with low nanomolar affinity for CD59. Through X-ray crystallographic studies and structure-activity relationship (SAR) studies, we identify key interactions that are essential for binding and activity. We find that the macrocyclic peptide CP-06 adopts a beta-hairpin structure and binds CD59 through an intermolecular beta-sheet, mimicking protein-protein interactions of biologically relevant CD59 interaction partners. We create dimeric and lipidated macrocyclic peptide conjugates as enhanced cell-active CD59 inhibitors and show that these probes can be used to modulate both complement-mediated killing of human cells and lytic activity of bacterial virulence factors. Together, our data provide a starting point for future development of macrocyclic peptides to target CD59 activity in diverse cellular contexts.

Indexed as

Bacterial ToxinsCD59 AntigensMacrocyclic CompoundsPeptidesPeptides, CyclicCrystallography, X-RayHumansStructure-Activity RelationshipBacterial ToxinsCD59 AntigensCD59 protein, humanMacrocyclic CompoundsPeptidesPeptides, CyclicCell‐surface receptorsMacrocyclic peptidesMembrane attack complexProtein‐protein interaction inhibitorsStructure‐guided design

Identifiers

PMID40272315
PMCPMC12207370

What OpenQuestion holds

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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.