Abstract
Bioactive peptides from amphibian skin secretions have attracted much attention from researchers because of their profound significance in novel drug development. Many amphibian skin-derived peptides have been proven to possess antimicrobial activity, anticancer activity as well as protease-inhibitory activity.In this study, a novel bioactive peptide with C-terminally amidation, SLRGCWTKSFPPQPCL-amide with a disulphide loop between Cys5 and Cys 15, was discovered from the skin secretion of the frog Rana chensinensis. Its cDNA precursor was obtained from the Rana chensinensis skin secretion by molecular cloning. The corresponding mature peptide, namely QUB-1817, was identified as an amphibian skin-derived Bowman-Birk inhibitor by bioinformatics approach for comparing the translated amino acid sequence from the cloned biosynthetic precursor-encoding cDNA sequence to the precursor cDNA sequence of Ranacylin-2CBa. Subsequently, the chemically-synthesised replicate was subjected to a series of bioassays. QUB-1817 exerted trypsin inhibitory activity with the Ki value of 0.389 μM and it only demonstrates haemolysis effect on mammalian erythrocytes within the concentration of 512 μM. However, there is no evidence to indicate that QUB-1817 has strong efficacy against three microorganisms: Gram-positive bacterium (S. aureus), Gram-negative bacterium (E. coli) and yeast (C. albicans). The minimum inhibitory concentrations of QUB-1817 against these three kinds of microorganisms were not detected even within the concentration of 512 μM. Additionally, this peptide could inhibit the proliferation of cancer cell lines including HCT116 and HT-29 at the concentration of 10 μM but did not show any inhibitory ability against MCF-7 and PC-3.
Thesis embargoed until 31st October 2024
| Date of Award | Dec 2019 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Tianbao Chen (Supervisor), Mei Zhou (Supervisor), Lei Wang (Supervisor) & Yuxin Wu (Supervisor) |