The hemolytic properties of the membrane modifying peptide antibiotics alamethicin, suzukacillin and trichotoxin.

Abstract

The membrane exciting peptide antibiotics alamethicin F-50 [56165-93-6], suzukacillin A [12712-80-0], and B [65216-22-0] and trichotoxin A-40 [65216-21-9] can be isolated from different strains of the fungus Trichoderma viride. Cultivation, isolation and purifn. procedures are described in detail for alamethicin F-50. At micromolar concns. the peptide antibiotics cause hemolysis in human erythrocytes, while at nanomolar levels they induce the formation of voltage-dependent pores of multi-state properties in black lipid membranes. A detailed study of the hemolytic action with variations of concn., temp. and incubation time revealed characteristic differences in the mode of hemolysis between the peptide antibiotics, which can be correlated with structural differences between these natural analogs. The addn. of bovine serum albumin reduces the hemolytic activity. The lytic action increases considerably from hypertonic to hypotonic media. For comparison the bee venom constituent melittin and sodium dodecylsulfate have been investigated under the same conditions. The lipophilic peptide antibiotics constitute a new class of membrane disrupting agents with particular properties not known from other lytic compds. Assuming that the lytic activity is proportional to the concn. of the peptide antibiotic, the temp. dependence of the concn./activity curves allows the calcn. of activation energies of 62 kJ/mol for alamethicin, 67 kJ/mol for suzukacillin A, and 79 kJ/mol for trichotoxin A-40. However, melittin revealed the very low activation energy of 49 kJ/mol. These values may be correlated with results from CD and 13C NMR expts. which indicate conformational changes of the peptides aggregating at the membrane/water interphase. [on SciFinder(R)]