Discovery of Dermaseptin-PC from frog skin secretion and rational design of broad-spectrum truncated analogues against both planktonic and sessile bacteria

    Research output: Contribution to conferencePoster


    View graph of relations

    Background: Antimicrobial peptides (AMPs) derived from the amphibian skin secretions are promising drug prototypes against ESKAPE strains. However, their clinical trials to date have shown efficacy only as topical agents, partly due to potential cytotoxicity. Material & Methods: Dermaseptin-PC (DM-PC) was discovered by the combination of ‘shotgun’ cloning and MS/MS fragmentation sequencing. Peptide design was carried out based on bioinformatics to enhance bio-efficacy and herapeutic index. The parent peptide and its analogues were synthesized using Tribute® synthesizer (Protein Technologies). The secondary structures of natural peptide and the analogues were validated by circular dichroism, and their antimicrobial efficacies were tested both on planktonic and sessile bacterial cells. Results: DM-PC possesses potent and broad-spectrum antimicrobial activity, but induce considerable haemolytic property that precludes it for further development. Here, truncated mimetics DMPC-19 and DMPC-10 were designed to improved selectivity against microorganisms. DMPC-19 maintained the activity and produced moderate haemolysis, while DMPC-10 shows significant decreases on both antimicrobial and haemolytic activities. Additionally, DMPC-10A, which contains Cha substituted at the C-terminus of DMPC-10, exhibits potent biological activity and higher therapeutic index. Moreover, DM-PC, DMPC-19 and DMPC-10A effectively inhibited the S.aureus and P. aeruginosa biofilms. Conclusion: With the optimisation of length of peptide chain and hydrophobicity, the therapeutic index can be improved. Additionally, the study of dermaseptin peptide also provides new insight on lead antibiotic drug discovery especially against Gram-negative bacteria and resistant strains.
    Original languageEnglish
    Number of pages1
    Publication statusPublished - 2018
    Event35th European Peptide Symposium - Dublin City University, Dublin, Ireland
    Duration: 26 Aug 201831 Aug 2018


    Conference35th European Peptide Symposium
    Abbreviated title35EPS
    Internet address

    ID: 158446131