Interaction of Syringomycin E Structural Analogues with Biological and Model Membranes

Abstract

Syringomycin E (SRE), a lipodepsinonapeptide produced by many Pseudomonas syringae pv. syringae strains, displays a prominent antifungal and haemolytic activity. The former is already exploited for post-harvest biocontrol of fruit and appears interesting in the perspective of medical applications; the latter hampers the use of this compound as a systemic drug. The ability to interact with biological membranes and form pores is at the basis of its biological activity. To gain insight into the structural features which are important for this process, we produced structural analogues of the metabolite and evaluated their activity on red blood cells and on artificial membranes of different compositions. The substitution of chlorine with hydrogen in the C-terminal amino acid caused a marked decrease in the pore-forming activity, in accordance with the previously observed trend in the antifungal activity assay. The cooperativity of the process is not affected, but the activity of the deschloro-SRE analogue (SREH) at difference from SRE, is not influenced by the presence of sterols in the artificial lipid bilayers. The residual activity of SREH is abolished when the lactone ring is hydrolysed. Thus, both the presence of chlorine in the C-terminal residue and the integrity of the macrocycle appear to be important for the pore-forming activity of SRE.