Synthesis of cyclic peptide antibiotics and related compounds

Abstract

The overuse of antibiotics has increase the resistance of bacteria to these compounds. Thus the need to develop new antibiotics has risen in the recent years. Antimicrobial peptides have become promising candidates for this issue. Polymyxin and murepavadin are among them, but are used only as last resource antibiotics. The aim of this work is to synthesise novel antibiotics that use these compound as scaffolds by solid phase peptide synthesis (SPPS). These analogues have been designed for improving their activity and reduce their toxicity. Secondly, the cyclization by a disulphide bond of these peptides has been studied as well as their impurities. Finally, these peptides have been purified by RP-HPLC and characterized by ESI mass spectroscopy. Furthermore, the antimicrobial activity of the analogues has been evaluated by minimum inhibitory concentration (MIC) determination. This research contributes into the development of novel antibiotics to combat multidrug-resistant bacteria