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Name

EF-Tu-binding Re-complexed antibiotics

Organization name

PROvendis GmbH

Profile

A series of novel Re(I)-(CO)3-N-heterocyclic carbene (NHC) complexes bearing unsubstituted benzimidazol-2-ylidene ligands as well as a variety of bisimine ligands has been prepared and comprehensively characterised. The complexes were found to exhibit potent antimicrobial activity against gram-positive bacterial strains in the low micromolar concentration range, rendering these compounds interesting lead structures for the development of novel metal-based antibiotic agents.

Anti-Gram-positive activity:
Substances have good activity against Bacillus subtilis and Staphylococcus aureus. Activity against MRSA strains were in the low and sub-micromolar range. No anti-Gram-negative activity was observed.

EF-Tu was identified as target in pull-down experiments using biotinylated compound. Protein biosynthesis inhibition was detected in precursor incorporation experiments using unlabeled compound.

Validated target:
Protein biosynthesis inhibition was observed and EF-Tu identified as target protein. Protein biosynthesis is a clinically validated target. Comparative proteomics studies suggest that the mechanism of action is different from known EF-Tu inhibitors.


Commercial Opportunities

The technology is offered for licensing and further therapeutic development.

Competitive Advantages

  • Novel antibiotic class
  • Activity against Gram-positive bacteria
  • Inhibits translation – a validated target

Current Status

In case of interest we are pleased to inform you about the patent Status.

Relevant Publication

Siegmund, D, et al. (2017) Benzannulated Re(I)-NHC complexes: synthesis, photophysical properties and antimicrobial activity. Dalton Trans. 46: 15269-79.

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