Mechanism of action of syringomycin structural analogues with model membranes

The toxicity of Pseudomonas syringae lipodepsinonapeptides is related to their ability to form pores in biological membranes and the activity is stronly dependent on the presence of chlorine in the C-terminal residue Thr(4-Cl). To evaluate the relevance of chlorine for the pore forming activity, the haemolytic activity of syringomycin and its deschloro analogue (SRH ) was compared. SRH was 75% less active than SR. The relevance of the macrocyclic structure was shown by comparing the activity of SRH and its linear derivative SRHL. Similar behaviour was also measured with liposomes with different lipid composition. It was shown that the presence of chlorine and the integrity of lacone ring are both important for the activity of syringomycin on model membranes