AbstractIn recent years, an increasingly number of bioactive peptides have been extracted from the skin secretion of Odorrana livida. Lividins are an important peptide family of AMPs for their multiple bioactivity aiming at microorganism killing, cancer diminishing or protease inhibiting. The research, therefore, will be focused mainly on the peptides isolated from the skin secretion of the amphibian Odorrana livida.
In this thesis, a novel bioactive peptide, QUB-1480 identified from the skin secretion of Odorrana livida was studied to both structure and bioactivities. The novel bioactive peptide QUB-1480 was obtained by ‘shotgun’ cloning of precursor-encoding cDNA, synthesised by solid-phase peptide synthesis (SPPS), purified utilizing RP-HPLC and confirmed using MALDI-TOF mass spectrometry. The antimicrobial, anticancer and protease inhibitory bioactivities were tested.
Consequently, QUB-1480 displayed protease inhibitory bioactivity with Ki value of 4.116 ± 10.66 µM. Meanwhile, no significant cytotoxicity to horse red blood cells was observed with QUB-1480 with a haemolysis of less than 4% at the concentration of 512 µM. Diminishing effect against E. coli was tested at the concentration of 256 µM. Besides, no significant antimicrobial bioactivity against S. aureus and C. albicans was tested. QUB-1480 showed anticancer bioactivity against HT29 cell line at the concentration of 0.5 mM. No significant anticancer bioactivity was tested against MCF-7, HCT-116 and PC-3 cell line.
Based on the results of peptide bioassays for QUB-1480, this novel peptide may have potency to be used as a therapeutic agent against human colon cancer. For the inhibitory activity against E. coli, more antimicrobial experiments against gram negative bacteria are expected to be done if possible. QUB-1480 could also be tested in vivo via some pharmaceutics. Meanwhile, QUB-1480 could be combined with other antimicrobial or anticancer agents to be used in the clinical therapy. Because of the inhibitory activity against E. coli, QUB-1480 is expected to lower the dose of the antibiotics to a large extent. At the same time, QUB-1480 may be used with colon cancer medicine such as Oxaliplatin to lower the side effects of traditional chemical medicine.
|Date of Award||Dec 2019|
|Supervisor||Tianbao Chen (Supervisor), Mei Zhou (Supervisor), Lei Wang (Supervisor) & Yuxin Wu (Supervisor)|