Due to the drug-resistant bacterial infections have become a global medical problem, antimicrobial peptides (AMPs) are considered as a new possibility to replace traditional antibiotics. Host-defense peptides in amphibians skins with various biological activities are a rich source for discovering new AMPs. This thesis amid to discover and functionally study a new AMP from the skin secretions of Rana amurensis. A cDNA encoding a new ranatuerin precursor was successfully established through molecular cloning and Sanger sequencing, and the mature peptide sequence of the active form, QUB-2566 (GVLKGVGKNVSGSLLHQLKCLISGGC), was deduced from the cloned cDNA. Thereafter, the corresponding synthetic peptide was obtained by solid-phase Fmoc synthesis, and its antibacterial activity, antiproliferative activity and haemolytic activity were tested. QUB-2566 was found to inhibit the growth of S. aureus and E. coli from a peptide concentration of 1µM; however, it required higher peptide concentration to completely inhibit the growth of these bacteria. Interesting, this peptide exhibited better bactericidal effect against E.coli (MBC=32 μM) than grampositive bacterium (S.aureus) (MBC=128 μM). Moreover, this peptide had less potency against C.albicans (MIC=512μM), along with low haemolytic activity (HC50< 512 μM). Also, peptide QUB-2566 had a weak antiproliferative effect on lung cancer cells H838. Altogether, this peptide may become a lead compound for new antimicrobial drug development because of its potent antibacterial potency against E.coli and low haemolytic activity.
|Date of Award||Dec 2020|
- Queen's University Belfast
|Supervisor||Lei Wang (Supervisor) & Mei Zhou (Supervisor)|