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Updated: Oct 3, 2025
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The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
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Metallo-β-Lactamase Inhibitor Phosphonamidate Monoesters
Katarzyna Palica1, Manuela Vorácová1, Susann Skagseth2
1Department of Chemistry-BMC, Organic Chemistry, Uppsala University, Husargatan 3, 752 37 Uppsala, Sweden.
ACS Omega
|February 14, 2022
Summary
New phosphonamidate monoesters show promise as therapeutics against metallo-β-lactamase-resistant bacteria. These compounds inhibit bacterial resistance mechanisms, potentially extending the life of existing antibiotics.
Area of Science:
- Medicinal Chemistry
- Microbiology
- Structural Biology
Background:
- Infectious diseases are a major global health concern, with antimicrobial resistance being a significant contributing factor.
- Bacterial resistance to β-lactam antibiotics, often mediated by metallo-β-lactamases, limits treatment options.
- Inhibiting metallo-β-lactamases could restore the efficacy of current antibiotics.
Purpose of the Study:
- To synthesize novel phosphonamidate monoesters.
- To evaluate their activity against metallo-β-lactamases (MBLs).
- To investigate their potential as a new class of antibiotics.
Main Methods:
- Synthesis of phosphonamidate monoesters.
- Assay of metallo-β-lactamase inhibition activity.
- Cytotoxicity studies.
- Nuclear Magnetic Resonance (NMR) spectroscopy for protein binding site determination.
- Expression and NMR assignment of single- and double-labeled NDM-1.
Main Results:
- Phosphonamidate monoesters were successfully synthesized.
- These compounds demonstrated metallo-β-lactamase inhibition activity.
- NMR studies elucidated the protein binding site of the inhibitors.
- NDM-1 expression and NMR assignment were achieved, aiding inhibitor development.
Conclusions:
- Phosphonamidate monoesters represent a promising new class of therapeutic agents.
- They show potential for combating bacteria resistant to metallo-β-lactamases.
- This research provides a foundation for developing next-generation antibiotics.
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