AbstractAntibiotics resistance has received much concern all over the world and even been regarded as one of the most challenging problems in medicine. This has called for the discovery of new antimicrobial agents. Antimicrobial peptides, especially from amphibians, have been demonstrated to express significant biological activities such as inhibiting and killing pathogens and cancer cells. More and more investigations indicate that they are promising candidates.
In this project, the precursor-encoding cDNA sequence was constantly obtained by using “shotgun” cloning from the skin secretion of the Chinese piebald odorous frog, Odorrana schmackeri. After translation, the amino acid sequence of the novel peptide QUB-3229 was obtained, which shows strong similarity with Odorranains and Brevinin-2s. The peptide was synthesised by solid phase peptide synthesis (SPPS). Then the synthetic peptide was identified by high performance liquid chromatography (HPLC) and Matrix-assisted laser desorption/ionisation Time-of-flight (MALDI-TOF) mass spectrometry (MS). Subsequently, the antimicrobial activity of QUB-3229 was evaluated against the Gram-positive bacterium, Staphylococcus aureus (S. aureus), the Gram-negative bacterium, Escherichia coli (E. coli) and the fungi, Candida albicans (C. albicans). The minimal inhibitory concentration (MIC) values were 16, 8 and 32 μM, respectively. The peptide showed bactericidal activities against the bacteria, but not against the fungi even at the highest tested concentration. The 10% haemolytic concentration (HC10) of QUB-3229 was 15.3 μM, which demonstrated that the effective concentration against E. coli was in the safety margin. The peptide did not display inhibitory ability in cancer cells.
Though the antimicrobial potency of QUB-3229 is not strong enough, it is expected that the discovery and obtained results of QUB-3229 may inspire the development of new drugs against common pathogens.
|Date of Award||Jul 2018|
|Supervisor||Lei Wang (Supervisor), Mei Zhou (Supervisor), Lei Li (Supervisor), Tianbao Chen (Supervisor) & Christopher Shaw (Supervisor)|