Science Pool

Corramycin: Enlarging the Antibacterial Spectrum

“Corramycin is a novel zwitterionic peptide with antibiotic properties. However, being mainly active against E. coli, Corramycin interest as a starting point for a new antibacterial program was challenging despite a promising activity in an E. coli septicemia/peritonitis animal model. We postulated that Corramycin spectrum could be improved if bacterial penetration could be enhanced.

In this poster we:

  • Identify the key amino acids by an Alascan strategy and then stabilize with key modifications
  • Improve in vitro activity and enlarge spectrum against key Gram-negative bacteria with a siderophore strategy
  • Remove genotoxicity alert (micronucleus alert) by a series of chemical modifications
  • Demonstrate improved in vivo efficacy in an E.coli septicemia model and a K.pneumoniae lung model compared to native Corramycin

This chemical program of >800 derivatives synthesized showed the benefits of vectorization to enlarge spectrum and to improve potency of modestly active antibacterials, as well as the need of a careful molecular design to solve issues such as the resistance risk and metabolic instability.

Read our poster to learn more about our research!