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Cyclization of the Antimicrobial Peptide Gomesin with Native Chemical Ligation: Influences on Stability and Bioactivity

Authors

  • Dr. Lai Yue Chan,

    1. The University of Queensland, Institute for Molecular Bioscience, 306 Carmody Road, Brisbane 4072 (Australia)
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  • Veronica M. Zhang,

    1. Australian Army Malaria Institute and The University of Queensland, Weary Dunlop Drive, Enoggera, Brisbane 4051 (Australia)
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  • Dr. Yen-hua Huang,

    1. The University of Queensland, Institute for Molecular Bioscience, 306 Carmody Road, Brisbane 4072 (Australia)
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  • Dr. Norman C. Waters,

    1. Australian Army Malaria Institute and The University of Queensland, Weary Dunlop Drive, Enoggera, Brisbane 4051 (Australia)
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  • Dr. Paramjit S. Bansal,

    1. Australian Nuclear Science and Technology Organization, New Illawarra Road, Lucas Heights, New South Wales 2234 (Australia)
    2. School of Pharmacy and Molecular Sciences and Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, McGregor Road, Smithfield, Queensland 4878 (Australia)
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  • Prof. David J. Craik,

    1. The University of Queensland, Institute for Molecular Bioscience, 306 Carmody Road, Brisbane 4072 (Australia)
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  • Prof. Norelle L. Daly

    Corresponding author
    1. The University of Queensland, Institute for Molecular Bioscience, 306 Carmody Road, Brisbane 4072 (Australia)
    2. School of Pharmacy and Molecular Sciences and Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, McGregor Road, Smithfield, Queensland 4878 (Australia)
    • The University of Queensland, Institute for Molecular Bioscience, 306 Carmody Road, Brisbane 4072 (Australia)
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Abstract

Gomesin is an 18-residue peptide originally isolated from the hemocytes of the Brazilian spider Acanthoscurria gomesiana. A broad spectrum of bioactivities have been attributed to gomesin, including in vivo and in vitro cytotoxicity against tumour cells, antimicrobial, antifungal, anti-Leishmania and antimalarial effects. Given the potential therapeutic applications of gomesin, it was of interest to determine if an engineered version with a cyclic backbone has improved stability and bioactivity. Cyclization has been shown to confer enhanced stability and activity to a range of bioactive peptides and, in the case of a cone snail venom peptide, confer oral activity in a pain model. The current study demonstrates that cyclization improves the in vitro stability of gomesin over a 24 hour time period and enhances cytotoxicity against a cancer cell line without being toxic to a noncancerous cell line. In addition, antimalarial activity is enhanced upon cyclization. These findings provide additional insight into the influences of backbone cyclization on the therapeutic potential of peptides.

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