Design of a novel membrane-destabilizing peptide selectively acting on acidic liposomes.
The design of amphipathic peptides resulted in a novel peptide with a selective ability to destabilize lipid bilayers of acidic liposomes. The newly synthesized peptide, termed mast 21, is a 21-residue long amino acid chain and can only act effectively on acidic liposomes lacking cholesterol. Moreover, mast 21 killed gram-positive and gram-negative bacteria, and it had no hemolytic activity. The antimicrobial and hemolytic activities paralleled the results of membrane destabilizing activity using liposomes. Circular dichroism and Trp-fluorescence emission spectra showed changes in the peptide conformation and circumstances around the peptide during interaction with liposomes. These changes were consistent with an increased alpha-helical content and a less polar environment for the tryptophan residue of the peptide. Mast 21 was observed under dark-field microscopy in real time attacking liposomes. Acidic liposomes were attacked, which resulted in peeling of the lipid bilayer with its subsequent destruction.
Machida
S
S
National Food Research Institute, Ministry of Agriculture, Forestry, and Fishery, Tsukuba, Ibaraki, Japan. lili@nfri.affrc.go.jp
Niimi
S
S
Shi
X
X
Ando
Y
Y
Yu
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D002942:Circular Dichroism; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006461:Hemolysis; D008051:Lipid Bilayers; D008081:Liposomes; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000138:chemical synthesis*; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D005452:Fluoresceins; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D011506:Proteins; C414743:mast 21 peptide; C007740:fluorexon