title: Linear bactenecin analogs with cell selectivity and anti-endotoxic activity.
abstract: Bactenecin (Bac) is a 12-residue disulfide-linked antimicrobial peptide isolated from the granules of bovine neutrophils. In this study, to develop novel linear Bac analogs with cell selectivity and anti-endotoxic activity, we designed and synthesized a series of linear Bac analogs with amino acid substitution in Cys3,11 and/or Val6,7 of Bac. Among Bac analogs, some analogs (Bac-W, Bac-KW, Bac-L, Bac-KL, Bac-LW, and Bac-KLW) with higher hydrophobicity showed the amalgamated property of cell selectivity and anti-endotoxic activity. Furthermore, Bac-W, Bac-KW, Bac-LW, and Bac-KLW showed serum stability comparable with that of disulfide-bonded Bac. Therefore, these Bac analogs (Bac-W, Bac-KW, Bac-LW, and Bac-KLW) can serve as promising antibiotics for the development of therapeutic agents for treatment against endotoxic shock and bacterial infection. In addition, our results suggest that a little increase in hydrophobicity may be responsible for the decreased cell selectivity of the multiple Arg-containing peptides (Bac-W, Bac-L, and Bac-LW) over the multiple Lys-containing peptides (Bac-KW, Bac-KL, and Bac-KLW).
authors.affiliation: Department of Bio-Materials, Graduate School, Chosun University, Gwangju, 501-759, Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hai Nan
authors.forename: Binu
authors.initials: B
authors.lastname: Jacob
authors.forename: Yangmee
authors.initials: Y
authors.lastname: Kim
authors.forename: Song
authors.initials: S
authors.lastname: Yub Shin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009569:Nitric Oxide / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C056454:bactenecin; D009569:Nitric Oxide
keywords: anti-endotoxin activity; cell selectivity; linear bactenecin analogs; serum stability