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@ARTICLE{Gulys:626511,
author = {Gulyás, Kinga Virág and Zhou, Liping and Salamonsen,
Daniel and Prester, Andreas and Bartels, Kim and Bosman,
Robert and Haffke, Paul and Li, Jintian and Tamási, Viola
and Deufel, Fritz and Thoma, Johannes and Andersson
Rasmussen, Anna and Csala, Miklós and Schroder Leiros,
Hanna-Kirsti and Xu, Zhijian and Widersten, Mikael and
Rohde, Holger and Schulz, Eike and Zhu, Weiliang and
Erdélyi, Máté},
title = {{D}ynamically chiral phosphonic acid-type
metallo-β-lactamase inhibitors},
journal = {Communications chemistry},
volume = {8},
number = {1},
issn = {2399-3669},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {PUBDB-2025-01464},
pages = {119},
year = {2025},
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.},
cin = {EMBL-User},
ddc = {540},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3) / DFG project
G:(GEPRIS)458246365 - Zeitaufgelöste Strukturanalysde der
extended spectrum Beta-Lactamase CTX-M-14 (458246365)},
pid = {G:(DE-HGF)POF4-6G3 / G:(GEPRIS)458246365},
experiment = {EXP:(DE-H253)P-P14-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40253435},
UT = {WOS:001471182500001},
doi = {10.1038/s42004-025-01510-5},
url = {https://bib-pubdb1.desy.de/record/626511},
}