Modulation of membrane activity of amphipathic, antibacterial peptides by slight modifications of the hydrophobic moment

FEBS Letters

Krause, Eberhard¹  Beyermann, Michael¹  MacDonald, Dorothy L²  Wieprecht, Torsten¹  Dathe, Margitta¹  Maloy, W.Lee²  Bienert, Michael¹ 

[1] Forschungsinstitut für Molekulare Pharmakologie, Alfred-Kowalke-Str. 4, D-10315 Berlin, Germany;Magainin Pharmaceuticals, Inc., 5110 Campus Drive, Plymouth Meeting, PA 19462, USA

关键词: Antibacterial peptide;    Antimicrobial peptide;    Amphipathic helix;    Hydrophobic moment;    Magainin;    μ;    hydrophobic moment;    Tris;    tris(hydroxymethyl)aminomethane;    CD;    circular dichroism;    SUVs;    small unilamellar vesicles;    LUVs;    large unilamellar vesicles;    MIC;    minimum inhibitory concentration;    M2a;    magainin 2 amide;    POPC;    1-palmitoyl-2-oleoylphosphatidylcholine;    POPG;    1-palmitoyl-2-oleoylphosphatidyl-dl-glycerol;    PC;    phosphatidylcholine;   

DOI  :  10.1016/S0014-5793(97)01266-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Starting from the sequences of magainin 2 analogs, peptides with slightly increased hydrophobic moment (μ) but retained other structural parameters were designed. Circular dichroism investigations revealed that all peptides adopt an α-helical conformation when bound to phospholipid vesicles. Analogs with increased μ 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.

【 授权许可】

Unknown