Design of a novel membrane-destabilizing peptide selectively acting on acidic liposomes

The design of amphipathic peptides resulted in a novel peptide with a selec tive ability to destabilize lipid bilayers of acidic liposomes. The newly s ynthesized peptide, termed mast 21, is a 21-residue long amino acid chain a nd can only act effectively on acidic liposomes lacking cholesterol. Moreov er, mast 21 killed Grampositive and Gram-negative bacteria, and it had no h emolytic activity. The antimicrobial and hemolytic activities paralleled th e results of membrane destabilizing activity using liposomes. Circular dich roism and Trp-fluorescence emission spectra showed changes in the peptide c onformation and circumstances around the peptide during interaction with li posomes. These changes were consistent with an increased alpha-helical cont ent and a less polar environment for the tryptophan residue of the peptide. Mast 21 was observed under dark-field microscopy in real time attacking li posomes. Acidic liposomes were attacked, which resulted in peeling of the l ipid bilayer with its subsequent destruction.