title: Synthesis, antimicrobial activity and toxicity of analogs of the scorpion venom BmKn peptides.
abstract: Two analogs of the natural peptide BmKn1 and four of BmKn2 found in the venom of the scorpion Buthus martensii Karsh have been synthesized and tested to compare their antimicrobial and hemolytic activity with the natural ones. Modifications of the natural sequence were done on the hydrophobic side of the alpha helix by increasing the size and hydrophobicity of the residues with alanine (BmKn2A1), valine (BmKn2V1) and leucine (BmKn2L1) respectively, and on the hydrophilic side by increasing the charge from +2 to +3 with two lysines (BmKn2K7). In order to study observed peptide aggregation, two peptides with one (BmKn1-6Lys) and two (BmKn1L2K2) positive charges respectively in the hydrophobic side have been also designed. Results show that the valine substituted analog BmKn2V1 and lysine substituted analog BmKn2K7 have in general, the highest antibiotic and hemolytic activity of the group. Introduction of one positive charge on the hydrophobic side shows a significant increase in antibacterial activity compared with the original sequence except for Bacillus and Enterobacter where, unexpectedly, the activity flats-off. In contrast, the analog with two positive charges has minimal antibacterial or hemolytic activity.
authors.affiliation: Department of Chemistry, Rhodes College, 2000 North Parkway, Memphis TN 38112, USA. Electronic address: saludbear@rhodes.edu.
authors.forename: Roberto de la Salud
authors.initials: Rde L
authors.lastname: Bea
authors.affiliation: Department of Chemistry, Rhodes College, 2000 North Parkway, Memphis TN 38112, USA.
authors.forename: Adam Fine
authors.initials: AF
authors.lastname: Petraglia
authors.affiliation: Department of Biology, Rhodes College, 2000 North Parkway, Memphis TN 38112, USA.
authors.forename: Laura Elena Luque de
authors.initials: LE
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001409:Bacillus cereus / Q000187:drug effects / Q000378:metabolism; D002942:Circular Dichroism; D021902:Enterobacter aerogenes / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D017433:Protein Structure, Secondary; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism; D012604:Scorpion Venoms / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D012605:Scorpions / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014270:Trifluoroethanol / Q000737:chemistry; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C444319:BmKn1 peptide; D012604:Scorpion Venoms; D014270:Trifluoroethanol; D014633:Valine; D008239:Lysine
keywords: Alpha-helix; Amphipathic; Antimicrobial peptides; Hemolysis