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

Implementation period
26.06.2023. – 25.06.2026.
Project Coordinator
Francesc Rabanal, University of Barcelona, Spain
Matilda Bäckberg, RISE Research Institutes of Sweden, Sweden
Pawel Baranczewski, Uppsala University, Sweden
Timothy R Walsh, University of Oxford, United Kingdom
Edgars Liepinsh, Latvian Institute of Organic Synthesis, Latvia
Carina Vingsbo-Lundberg, Statens Serum Institute, Denmark
Klaus Skovbo Jensen, CANDOR Simulation, Denmark
Total costs
€ 1 510 899
Costs for Latvian partner
€ 300 000
About MURYXIN project

The 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.