Helical peptoid mimics of magainin-2 amide.
A series of peptoid oligomers were designed as helical, cationic, and facially amphipathic mimics of the magainin-2 amide antibacterial peptide. We used circular dichroism spectroscopy to determine the conformation of these peptoids in aqueous buffer and in the presence of bacterial membrane-mimetic lipid vesicles, composed of a 7:3 mol ratio of POPE:POPG. We found that certain peptoids, which displayed characteristically helical CD in buffer and lipid vesicles, exhibit selective (nonhemolytic) and potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In contrast, peptoids that exhibit weak CD, reminiscent of that of a peptide random coil, were ineffective antibiotics. In a manner similar to the natural magainin peptides, we find a correlation between peptoid lipophilicity and hemolytic propensity. We observe that a minimum length of approximately 12 peptoid residues may be required for antibacterial activity. We also see evidence that a helix length between 24 and 34 A may provide optimal antibacterial efficacy. These results provide the first example of a water-soluble, structured, bioactive peptoid.
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002412:Cations; D002942:Circular Dichroism; D015195:Drug Design; D005998:Glycine / Q000031:analogs & derivatives; D006461:Hemolysis / Q000187:drug effects; D054806:Magainins; D008826:Microbial Sensitivity Tests; D017433:Protein Structure, Secondary; D029867:Xenopus Proteins
D000577:Amides; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002412:Cations; D054806:Magainins; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; D005998:Glycine