Antimicrobial Peptides from Venom: Structure, Function and Toxicity

RAWSON, Kirstie Marie (2019). Antimicrobial Peptides from Venom: Structure, Function and Toxicity. Doctoral, Sheffield Hallam University.

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Link to published version:: https://doi.org/10.7190/shu-thesis-00294
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    Abstract

    The need for new antimicrobials with novel mechanisms of action is becoming one of the most urgent requirements in modern medicine. Antimicrobial peptides (AMPs) are naturally occurring compounds which possess a rapid killing mechanism and low resistance potential. Consequently, they are being viewed as potential alternatives to traditional antibiotics. One of the major factors limiting further development of AMPs is off target toxicity. Enhancements to antimicrobial peptides which can maximise antimicrobial activity whilst reducing mammalian cytotoxicity would make these peptides more attractive as future pharmaceuticals. Smp24 and Smp43 are AMPs derived from the venom of the scorpion Scorpio maurus palmatus. This study sought to better understand the relationship between structure, function and bacterial selectivity of these peptides by performing single amino acid substitutions. The structure-function relationship of the two AMPs has been investigated by performing N-terminal, mid-chain and Cterminal amino acid substitutions and determining the effect this has on the antimicrobial and cytotoxic activity of the peptides. The structural implications of the amino acid substitutions have been investigated via homology modelling and circular dichroism spectroscopy. Functional improvements have been made to modified peptides when compared with native Smp24 and native Smp43, which have produced peptides with enhanced therapeutic indices.

    Item Type: Thesis (Doctoral)
    Additional Information: Director of studies: Keith Miller
    Research Institute, Centre or Group - Does NOT include content added after October 2018: Sheffield Hallam Doctoral Theses
    Identification Number: https://doi.org/10.7190/shu-thesis-00294
    Depositing User: Colin Knott
    Date Deposited: 12 Aug 2020 14:57
    Last Modified: 12 Aug 2020 15:00
    URI: http://shura.shu.ac.uk/id/eprint/26934

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