Modulation of membrane activity of amphipathic, antibacterial peptides by slight modifications of the hydrophobic moment.
Starting from the sequences of magainin 2 analogs, peptides with slightly increased hydrophobic moment (mu) but retained other structural parameters were designed. Circular dichroism investigations revealed that all peptides adopt an alpha-helical conformation when bound to phospholipid vesicles. Analogs with increased mu were considerably more active in permeabilizing vesicles mainly composed of zwitterionic lipid. In addition, the antibacterial and hemolytic activities of these analogs were enhanced. Correlation of permeabilization and binding indicated that the activity increase is predominantly caused by an increased membrane affinity of the peptides due to strengthened hydrophobic interactions.
Wieprecht
T
T
Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany. wieprecht@fmp-berlin.de
Dathe
M
M
Krause
E
E
Beyermann
M
M
Maloy
W L
WL
MacDonald
D L
DL
Bienert
M
M
D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D006801:Humans; D050356:Lipid Metabolism; D054806:Magainins; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D029867:Xenopus Proteins
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054806:Magainins; D010455:Peptides; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus