The discovery and bioactivity evaluation of a novel peptide, QUB-1925, and its modified analogue, QUB-2067, from the defensive skin secretion of the frog, Phyllomedusa coelestis

As a result of decades of research on frog skin secretions, a great number of bioactive frog skin peptides have been isolated and structurally characterised. These bioactive frog skin peptides, which play a crucial role in protecting frogs from pathogenic microbes’ invasion and natural predators’ attack, are thought to be highly potential of being or providing lead compounds in the future drug development. Those frog skin antimicrobial peptides with potent activities against a broad range of microorganisms are of highest potential, due to the emergence of the multiple drug resistance issue of conventional antibiotics.<br/>In this research, a novel bioactive peptide, named QUB-1925, was identified and structurally-characterised from the lyophilised skin secretion of the frog, Phyllomedusa coelestis. The ‘shotgun’ cloning strategy was applied to obtain the peptide precursor sequence. According to the mature peptide sequence, a synthetic replicate of QUB-1925 was obtained using the solid-phase peptide synthesis (SPPS) method. Then the synthetic replicate of QUB-1925 was subjected to bioactivity and toxicity tests. Finally, QUB-1925 was found to have no potent antimicrobial activity against tested microorganisms but to have haemolytic activity at high concentrations. Thus, QUB-1925 was structurally modified to create an analogue named QUB-2067. This modified peptide QUB-2067 displayed potent activities against all tested microorganisms, namely S. aureus (MIC = 64 μM; MBC = 128 μM), E. coli (MIC = 32 μM; MBC = 64 μM) and C. albicans (MIC = 16 μM; MBC = 16 μM) and the haemolytic activity of QUB-2067 was weaker than that of QUB-1925.<br/>

Name dc:type.qualificationname

Master of Philosophy

Level dc:type.qualificationlevel

Masters Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2017

Author dc:creator

• He, Mengting

Advisors dc:contributor.advisor

• Chen, Tianbao
• Wang, Lei
• Zhou, Mei

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/6e88b07b-fb67-48e6-a804-8ce1e846a8b2

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/6e88b07b-fb67-48e6-a804-8ce1e846a8b2