Evidence map›Paper›PMID 40138381›Full record

ArticleAngewandte Chemie (International ed. in English)2025

Antimicrobial Peptide-Peptoid Macrocycles from the Polymyxin B2 Chemical Space.

Etienne Bonvin, Markus Orsi, Thierry Paschoud, Ashvin Gopalasingam, Jérémie Reusser, Thilo Köhler, Christian van Delden, Jean-Louis Reymond

Abstract 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. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Antimicrobial Peptide-Peptoid Macrocycles from the Polymyxin B2 Chemical Space.Angewandte Chemie (International ed. in English) · 2025
    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.

Etienne BonvinDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, CH-3012, Switzerland.
Markus OrsiDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, CH-3012, Switzerland.
Thierry PaschoudDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, CH-3012, Switzerland.
Ashvin GopalasingamDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, CH-3012, Switzerland.
Jérémie ReusserDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, CH-3012, Switzerland.
Thilo KöhlerDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, CH-1211, Switzerland.
Christian van DeldenDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, CH-1211, Switzerland.
Jean-Louis ReymondDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, CH-3012, Switzerland.

Funding

H2020 European Research Council 885076Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 200020_207976
6 · The paper itself

Abstract

Macrocycles have emerged as important new modalities in drug discovery. In the context of addressing the global threat of antimicrobial resistance, here we used a genetic algorithm as a computational tool to evolve peptide-peptoid macrocycles to resemble polymyxin B2 (PMB2), a macrocyclic lipopeptide natural product used as last resort antibiotic. Synthesis and testing of 41 PMB2 analogs revealed several peptide-peptoid macrocycles showing strong, although salt sensitive, activity against Escherichia coli and multidrug-resistant strains of Pseudomonas aeruginosa, high serum stability, and lower toxicity to kidney cells compared to PMB2. These macrocycles resembled PMB2 in terms of outer membrane permeabilization, inner membrane depolarization, lipopolysaccharide binding, and loss of activity when linearized, but, unlike PMB2, induced aggregation of intracellular contents, an effect was reported for other antimicrobial peptoids. These experiments exemplify a combined computational and experimental approach which might be generally useful to explore the chemical space of macrocyclic peptide natural products.

Indexed as

Anti-Bacterial AgentsAntimicrobial PeptidesPeptoidsPolymyxin BEscherichia coliHumansMicrobial Sensitivity TestsPseudomonas aeruginosaAnti-Bacterial AgentsAntimicrobial PeptidesPeptoidsPolymyxin BAntimicrobialsChemical spaceMacrocyclesNatural productsPeptoids

Identifiers

PMID40138381
PMCPMC12124432

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.