A novel linear amphipathic beta-sheet cationic antimicrobial peptide with enhanced selectivity for bacterial lipids
| Autor: | Jack Blazyk, Janet L. Hammer, Russell Wiegand, U. Prasad Kari, W. Lee Maloy, Jason Klein, Raquel F. Epand, Richard M. Epand |
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| Rok vydání: | 2001 |
| Předmět: |
Circular dichroism
Protein Conformation Molecular Sequence Data Beta sheet Peptide Biochemistry Hemolysis Protein Structure Secondary chemistry.chemical_compound Phosphatidylcholine Amphiphile Spectroscopy Fourier Transform Infrared Animals Amino Acid Sequence Molecular Biology chemistry.chemical_classification Phosphatidylethanolamine Phosphatidylglycerol Bacteria Calorimetry Differential Scanning Circular Dichroism Tryptophan Lipid metabolism Phosphatidylglycerols Cell Biology Fluoresceins Lipid Metabolism Anti-Bacterial Agents Spectrometry Fluorescence chemistry Biophysics Phosphatidylcholines Peptides |
| Zdroj: | The Journal of biological chemistry. 276(30) |
| ISSN: | 0021-9258 |
| Popis: | All known naturally occurring linear cationic peptides adopt an amphipathic alpha-helical conformation upon binding to lipids as an initial step in the induction of cell leakage. We designed an 18-residue peptide, (KIGAKI)3-NH2, that has no amphipathic character as an alpha-helix but can form a highly amphipathic beta-sheet. When bound to lipids, (KIGAKI)3-NH2 did indeed form a beta-sheet structure as evidenced by Fourier transform infrared and circular dichroism spectroscopy. The antimicrobial activity of this peptide was compared with that of (KIAGKIA)3-NH2, and it was better than that of GMASKAGAIAGKIAKVALKAL-NH2 (PGLa) and (KLAGLAK)3-NH2, all of which form amphipathic alpha-helices when bound to membranes. (KIGAKI)3-NH2 was much less effective at inducing leakage in lipid vesicles composed of mixtures of the acidic lipid, phosphatidylglycerol, and the neutral lipid, phosphatidylcholine, as compared with the other peptides. However, when phosphatidylethanolamine replaced phosphatidylcholine, the lytic potency of PGLa and the alpha-helical model peptides was reduced, whereas that of (KIGAKI)3-NH2 was improved. Fluorescence experiments using analogs containing a single tryptophan residue showed significant differences between (KIGAKI)3-NH2 and the alpha-helical peptides in their interactions with lipid vesicles. Because the data suggest enhanced selectivity between bacterial and mammalian lipids, linear amphipathic beta-sheet peptides such as (KIGAKI)3-NH2 warrant further investigation as potential antimicrobial agents. |
| Databáze: | OpenAIRE |
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