Abstract
Based on extensive natural drug investigations, frog skin has been found to be a rich source of biologically active compounds, especially the broad-spectrum antimicrobial peptides, which have attracted increasing attention as potential therapeutic agents.In this thesis, a novel bioactive peptide was discovered in the skin secretion of Rana amurensis. This skin secretion was collected by mild electrical stimulation and used to isolate mRNA for the establishment of a cDNA library. “Shotgun” cloning was employed to obtain the peptide precursor-encoding cDNA sequence and the mature peptide structure was deduced from this cloned cDNA. A sufficient quantity of a peptide replicate for bioactivity testing, was synthesised by solid-phase peptide synthesis (SPPS).
After these tests, QUB-2274 was found to exhibit differential growth-inhibitory activity towards the Gram-positive bacterium S.aureus, the Gram-negative bacterium E.coli, and the yeast C.albicans, but with a high haemolytic activity. It also had a strong anti-proliferative effect on the four tested human cancer cell lines: PC-3, NCI-H157, MDA-MB-435S and U251MG.
These studies on QUB-2274, have provided the basic data for research on a bioactive peptide from an amphibian. Unlike conventional antibiotics, the antimicrobial peptides (AMPs) are less likely to cause drug resistance. If QUB-2274 is to be considered for application in the clinic, its high haemolytic activity requires addressing such as by rational analogue design.
| Date of Award | 2017 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Tianbao Chen (Supervisor), Lei Wang (Supervisor), Lei Li (Supervisor) & Mei Zhou (Supervisor) |