There is an urgent need for new antimicrobial agents to treat infections caused by pathogens that are increasingly resistant to current antibiotics.
Telomycin (SAR138178) is a natural cyclic depsipeptide isolated from culture of Streptomyces species. It is bactericidal against some Gram-positive bacteria and is not cytotoxic. Its complex structure is composed of a ring of 9 amino-acids and a lateral chain of two amino-acids including an iso-aspartic moeity. Telomycin was obtained by fermentation in sufficient quantities to prepare semi-synthetic derivatives.
Preliminary semi-synthetic explorations led to improvement of antibacterial activities by derivatization of the iso-aspartic residue. However, solubility was poor and strong serum / surfactant effects were observed with these modifications. Introduction of carbohydrate moeities on the lateral chain was envisaged to overcome these issues.
Here, we report the synthesis and antibacterial activities of these new glycolipopeptides
