%0 Journal Article
%A Gulyás, Kinga Virág
%A Zhou, Liping
%A Salamonsen, Daniel
%A Prester, Andreas
%A Bartels, Kim
%A Bosman, Robert
%A Haffke, Paul
%A Li, Jintian
%A Tamási, Viola
%A Deufel, Fritz
%A Thoma, Johannes
%A Andersson Rasmussen, Anna
%A Csala, Miklós
%A Schroder Leiros, Hanna-Kirsti
%A Xu, Zhijian
%A Widersten, Mikael
%A Rohde, Holger
%A Schulz, Eike
%A Zhu, Weiliang
%A Erdélyi, Máté
%T Dynamically chiral phosphonic acid-type metallo-β-lactamase inhibitors
%J Communications chemistry
%V 8
%N 1
%@ 2399-3669
%C [London]
%I Macmillan Publishers Limited, part of Springer Nature
%M PUBDB-2025-01464
%P 119
%D 2025
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40253435
%U <Go to ISI:>//WOS:001471182500001
%R 10.1038/s42004-025-01510-5
%U https://bib-pubdb1.desy.de/record/626511