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Updated: Dec 13, 2025

The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
08:06

The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions

Published on: February 1, 2018

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Structure-based design of covalent inhibitors targeting metallo-β-lactamases

Cheng Chen1, Ke-Wu Yang1

  • 1Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, 1 Xuefu Avenue, Xi'an, 710127, PR China.

European Journal of Medicinal Chemistry
|July 25, 2020
PubMed

Insights

Metallo-β-lactamases (MβLs) confer bacterial resistance to antibiotics. This review details covalent inhibitors and design strategies for developing new therapeutics against these dangerous enzymes.

Area of Science:

  • Microbiology
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Metallo-β-lactamases (MβLs) are a significant threat to global health, mediating bacterial resistance to nearly all β-lactam antibiotics.
  • Despite their clinical importance, no MβL inhibitors are currently available in clinics.

Purpose of the Study:

  • To review common covalent targets in B1 and B2 MβLs.
  • To summarize covalent inhibitors and their inhibition modes as of 2020.
  • To highlight rational design strategies for MβL inhibitors and dual-action MβL/serine β-lactamase (SβL) inhibitors.

Main Methods:

  • Literature review of MβL inhibitors and their mechanisms.
  • Analysis of crystal structures for rational inhibitor design.
  • Exploration of dual-action inhibitor development targeting MβL lysine and SβL serine residues.

Main Results:

  • Identification of common covalent targets in MβLs.
  • Compilation of known covalent MβL inhibitors and their inhibition modes up to 2020.
  • Demonstration of rational design principles and dual-action inhibitor potential.

Conclusions:

  • Covalent inhibition offers a promising strategy against MβLs.
  • Structure-guided design and dual-action inhibitors are key for future therapeutic development.
  • Understanding covalent inhibition mechanisms is crucial for advancing MβL-targeted therapies.
Keywords:
Antibiotic resistanceCovalent inhibitorMetallo-β-lactamases

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