Cationic hydrophobic peptides with antimicrobial activity.
The MICs of cationic, hydrophobic peptides of the prototypic sequence KKAAAXAAAAAXAAWAAXAAAKKKK-amide (where X is one of the 20 commonly occurring amino acids) are in a low micromolar range for a panel of gram-negative and gram-positive bacteria, with no or low hemolytic activity against human and rabbit erythrocytes. The peptides are active only when the average segmental hydrophobicity of the 19-residue core is above an experimentally determined threshold value (where X is Phe, Trp, Leu, Ile, Met, Val, Cys, or Ala). Antimicrobial activity could be increased by using peptides that were truncated from the prototype length to 11 core residues, with X being Phe and with 6 Lys residues grouped at the N terminus. We propose a mechanism for the interaction between these peptides and bacterial membranes similar to the "carpet model," wherein the Lys residues interact with the anionic phospholipid head groups in the bacterial membrane surface and the hydrophobic core portion of the peptide is then able to interact with the lipid bilayer, causing disruption of the bacterial membrane.
Stark
Margareta
M
Division of Structural Biology and Biochemistry, Research Institute, Hospital for Sick Children, Toronto M5G 1X8, Canada.
Liu
Li-Ping
LP
Deber
Charles M
CM
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides; D011817:Rabbits
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D010455:Peptides