Shortened amoebapore analogs with enhanced antibacterial and cytolytic activity.
Amoebapores are cytolytic peptides of Entamoeba histolytica which function by the formation of ion channels in target cell membranes. Three isoforms (amoebapore A, B, and C) exist in amoebic cytoplasmic granules. They are composed of 77 amino acid residues arranged in four alpha-helical domains. In order to analyze the structure-function relationships, 15 synthetic peptides of 24-25 residues were constructed based on the assumption that the third helix is the membrane-penetrating domain and on the previous finding that positively charged residues are significant for activity. Activity of these short versions of amoebapores was determined towards artificial and natural targets, such as liposomes, bacteria, erythrocytes and a human tumor cell line. It was found that some of the novel peptides were highly active and showed a broader activity spectrum compared to the parent molecules.
Andrä
J
J
Department of Molecular Biology, Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany.
Berninghausen
O
O
Wülfken
J
J
Leippe
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D003603:Cytotoxins; D004058:Diffusion; D004748:Entamoeba histolytica / Q000737:chemistry*; D004912:Erythrocytes; D006801:Humans; D007473:Ion Channels; D008081:Liposomes; D008565:Membrane Proteins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured
D003603:Cytotoxins; D007473:Ion Channels; D008081:Liposomes; D008565:Membrane Proteins; D010455:Peptides; D015800:Protozoan Proteins; C041670:amoebapore proteins, protozoan