The disulfide bond as a chemical tool in cyclic peptide antibiotics: engineering disulfide polymyxins and murepavadin (MURYXIN)

Environment

Therapeutics

This project presents an innovative chemical tool to be applied to known cyclic peptide antibiotics.

The rationale of the design consists of maintaining the overall structure of the antibiotic to preserve the antibacterial activity while the presence of the chemical tool within the peptide backbone would facilitate the initial metabolization and detoxification by oxidorreductases upon eventual accumulation of the antibiotic in the kidney. The project follows a proof-of-concept scheme involving the necessary chemistry to prepare the model compounds, the in vitro and in vivo assays to assess activity and low toxicity, and estimate a therapeutic window. Finallly, tests to prove the design hypothesis and the mechanism of action at the membrane level are also proposed.

Project partners

  • Francesc Rabanal, Universitat de Barcelona, Spain (Coordinator)
  • Matilda B√§ckberg, RISE Research Institutes of Sweden, Sweden
  • Pawel Baranczewski, Uppsala University, Sweden
  • Edgars Liepinsh, Latvian Institute of Organic Synthesis, Latvia
  • Timothy R Walsh, University of Oxford, United Kingdom
  • Carina Vingsbo-Lundberg, Statens Serum Institut, Denmark
  • Klaus Skovbo Jensen, CANDOR Simulation, Denmark

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