Improving the therapeutic index of Smp24, a venom-derived antimicrobial peptide: increased activity against gram-negative bacteria

RAWSON, Kirstie M., LACEY, Melissa M., STRONG, Peter N. and MILLER, Keith (2022). Improving the therapeutic index of Smp24, a venom-derived antimicrobial peptide: increased activity against gram-negative bacteria. International Journal of Molecular Sciences, 23 (14): 7979.

[img]
Preview
PDF
ijms-23-07979.pdf - Published Version
Creative Commons Attribution.

Download (2MB) | Preview
Official URL: https://www.mdpi.com/1422-0067/23/14/7979
Open Access URL: https://www.mdpi.com/1422-0067/23/14/7979/pdf?vers... (Published version)
Link to published version:: https://doi.org/10.3390/ijms23147979
Related URLs:

    Abstract

    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. We have previously characterised Smp24, an AMP derived from the venom of the scorpion Scorpio maurus palmatus. This study sought to better understand the relationship between the structure, function and bacterial selectivity of this peptide by performing single amino acid substitutions. The antimicrobial, haemolytic and cytotoxic activity of modified Smp24 peptides was determined. The results of these investigations were compared with the activity of native Smp24 to determine which modifications produced enhanced therapeutic indices. The structure−function relationship of Smp24 was investigated by performing N-terminal, mid-chain and C-terminal amino acid substitutions and determining the effect that they had on the antimicrobial and cytotoxic activity of the peptide. Increased charge at the N-, mid- and C-termini of the peptide resulted in increased antimicrobial activity. Increased hydrophobicity at the N-terminus resulted in reduced haemolysis and cytotoxicity. Reduced antimicrobial, haemolytic and cytotoxic activity was observed by increased hydrophobicity at the mid-chain. Functional improvements have been made to modified peptides when compared with native Smp24, which has produced peptides with enhanced therapeutic indices.

    Item Type: Article
    Additional Information: ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 1422-0067 **History: published 20-07-2022; accepted 18-07-2022
    Uncontrolled Keywords: antimicrobial peptide, scorpion venom, peptide modification
    Identification Number: https://doi.org/10.3390/ijms23147979
    SWORD Depositor: Colin Knott
    Depositing User: Colin Knott
    Date Deposited: 26 Jul 2022 14:33
    Last Modified: 26 Jul 2022 14:33
    URI: http://shura.shu.ac.uk/id/eprint/30486

    Actions (login required)

    View Item View Item

    Downloads

    Downloads per month over past year

    View more statistics