Antibiotic activity of Leu-Lys rich model peptides.
To develop novel antibiotic peptides useful as therapeutic drugs, short model peptides rich in Leu and Lys were designed by changing not only the net positive charge by Lys-deletion but also in the hydrophobic helix region by Leu-deletion from a peptide analogue of cecropin A (1-8)-magainin 2 (1-12) (CA-MA) known as P5. In particular, one peptide (P6), which was obtained by deleting Lys residues (positions 1, 3, 5, 9, 10, 13, 14) and Leu residues (positions 4, 7, 8, 11, 12, 15) and keeping Pro (position 6) and Trp (position 2), showed a strong antimicrobial and antitumor activity at 0.2-3.1 microM without hemolytic activity against human erythrocyte cells. Furthermore, P6 causes significant morphological alterations of the bacterial surfaces at 3.1 microM as shown by scanning electron microscopy.
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000648:ultrastructure; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004912:Erythrocytes / Q000187:drug effects*; D005658:Fungi / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007930:Leucine / Q000737:chemistry* / Q000494:pharmacology*; D008239:Lysine / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009369:Neoplasms / Q000188:drug therapy*; D010446:Peptide Fragments
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D010446:Peptide Fragments; D007930:Leucine; D008239:Lysine