Linear bactenecin analogs with cell selectivity and anti-endotoxic activity

Authors

  • Yong Hai Nan,

    1. Department of Bio-Materials, Graduate School, Chosun University, Gwangju, Korea
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    • These authors contributed equally to this work.
  • Binu Jacob,

    1. Department of Bio-Materials, Graduate School, Chosun University, Gwangju, Korea
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    • These authors contributed equally to this work.
  • Yangmee Kim,

    1. Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea
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  • Song Yub Shin

    Corresponding author
    1. Department of Bio-Materials, Graduate School, Chosun University, Gwangju, Korea
    • Department of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju, Korea
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Song Yub Shin, Department of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju 501-759, Korea. E-mail: syshin@chosun.ac.kr

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). Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

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