Perpustakaan Digital ITB

Bombinin H2 and H4 are peptides isolated fromthe skin of the frogBombina variegatathat exhibit antimicrobialactivity againstLeishmaniaas well as bacteria. H4 is an isomerof H2 that hasD-allo-Ile at position 2 from the N-terminus.Although H4 exhibits higher antimicrobial activity than that ofH2, the molecular mechanism has remained unclear. In thisstudy, we tried to reveal the molecular mechanism in terms oflipid membrane disruption through pore formation, usingelectrophysiological measurements. Based on our experiments,we estimated the pore-forming structure, pore size, and thekinetics in a bacteria model membrane. Stochastic analysis ofthe current data indicated that peptide isomerization enables usto accelerate the pore formation owing to the higher affinitybetween the peptide and lipid membrane. Additionally, the H2/H4 mixture was studied with31P NMR and cross-linkingexperiment with mass spectrometry. It was found that heterogeneous pore formation with H2 and H4 was indicated. Thiselectrophysiological approach will likely be promising as a useful tool for analyzing the molecular mechanism of pore-formingpeptides.