TY  - JOUR
AU  - Gulyás, Kinga Virág
AU  - Zhou, Liping
AU  - Salamonsen, Daniel
AU  - Prester, Andreas
AU  - Bartels, Kim
AU  - Bosman, Robert
AU  - Haffke, Paul
AU  - Li, Jintian
AU  - Tamási, Viola
AU  - Deufel, Fritz
AU  - Thoma, Johannes
AU  - Andersson Rasmussen, Anna
AU  - Csala, Miklós
AU  - Schroder Leiros, Hanna-Kirsti
AU  - Xu, Zhijian
AU  - Widersten, Mikael
AU  - Rohde, Holger
AU  - Schulz, Eike
AU  - Zhu, Weiliang
AU  - Erdélyi, Máté
TI  - Dynamically chiral phosphonic acid-type metallo-β-lactamase inhibitors
JO  - Communications chemistry
VL  - 8
IS  - 1
SN  - 2399-3669
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - PUBDB-2025-01464
SP  - 119
PY  - 2025
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40253435
UR  - <Go to ISI:>//WOS:001471182500001
DO  - DOI:10.1038/s42004-025-01510-5
UR  - https://bib-pubdb1.desy.de/record/626511
ER  -