Evidence map›Paper›PMID 40253435›Full record

ArticleCommunications chemistry2025

Dynamically chiral phosphonic acid-type metallo-β-lactamase inhibitors.

Kinga Virág Gulyás, Liping Zhou, Daniel Salamonsen, Andreas Prester, Kim Bartels, Robert Bosman, Paul Haffke, Jintian Li, Viola Tamási, Fritz Deufel and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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. Article
  2. 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

20 authors.

Kinga Virág GulyásDepartment of Chemistry - BMC, Organic Chemistry and the Uppsala Antibiotic Center; Uppsala University, Uppsala, Sweden.
Liping ZhouDrug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Daniel SalamonsenDepartment of Chemistry, Faculty of Science and Technology, UiT The Arctic University of Norway, Tromsø, Norway.
Andreas PresterUniversity Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.ORCID http://orcid.org/0000-0003-2738-7682
Kim BartelsUniversity Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Robert BosmanUniversity Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Paul HaffkeUniversity Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Jintian LiDrug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Viola TamásiDepartment of Molecular Biology, Semmelweis University, Budapest, Hungary.
Fritz DeufelDepartment of Chemistry - BMC, Organic Chemistry and the Uppsala Antibiotic Center; Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-4910-3388
Johannes ThomaDepartment of Chemistry & Molecular Biology, Center for Antibiotic Resistance Research, CARe, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-3584-8274
Anna Andersson RasmussenLund Protein Production Platform, Lund, Sweden.
Miklós CsalaDepartment of Molecular Biology, Semmelweis University, Budapest, Hungary.ORCID http://orcid.org/0000-0002-3829-4361
Hanna-Kirsti Schroder LeirosDepartment of Chemistry, Faculty of Science and Technology, UiT The Arctic University of Norway, Tromsø, Norway.ORCID http://orcid.org/0000-0002-2726-6322
Zhijian XuDrug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-3063-8473
Mikael WiderstenDepartment of Chemistry - BMC, Organic Chemistry and the Uppsala Antibiotic Center; Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-3203-3793
Holger RohdeUniversity Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.ORCID http://orcid.org/0000-0001-8587-4433
Eike C SchulzUniversity Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.ORCID http://orcid.org/0000-0002-1685-8605
Weiliang ZhuDrug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0001-6699-5299
Máté ErdélyiDepartment of Chemistry - BMC, Organic Chemistry and the Uppsala Antibiotic Center; Uppsala University, Uppsala, Sweden. mate.erdelyi@kemi.uu.se.ORCID http://orcid.org/0000-0003-0359-5970

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibiotic resistance is a growing global health threat that risks the lives of millions. Among the resistance mechanisms, that mediated by metallo-β-lactamases is of particular concern as these bacterial enzymes dismantle most β-lactam antibiotics, which are our widest applied and cheapest to produce antibiotic agents. So far, no clinically applicable metallo-β-lactamase inhibitors are available. Aiming to adapt to structural variations, we introduce the inhibitor concept: dynamically chiral phosphonic acids. We demonstrate that they are straightforward to synthesize, penetrate bacterial membranes, inhibit the metallo-β-lactamase enzymes NDM-1, VIM-2 and GIM-1, and are non-toxic to human cells. Mimicking the transition state of β-lactam hydrolysis, they target the Zn ions of the metallo-β-lactamase active site. As a unique feature, both of their stereoisomers bind metallo-β-lactamases, which provides them unparalleled adaptability to the structural diversity of these enzymes, and may allow them to hamper bacteria's ability for resistance development.

Identifiers

PMID40253435
PMCPMC12009420

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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.