Identification and functional evaluation of a bioactive peptide, QUB-1942, from the skin secretion of Phyllomedusa hypochondrialis

Abstract

Amphibians have evolved a variety of defense mechanisms, including the production of poisonous or unpleasant skin secretions, to fend off intruding microbes and predators. In Traditional Chinese Medicine, many types of therapeutic compounds have long been sought from the skins of amphibians. There is an urgent need for new antibiotic resources, and current efforts need to be doubled at the very least, as more and more pathogenic bacteria are becoming resistant to commercial antibiotics while novel putative antibiotics continue to fail in this struggle with bacteria. Previous research has shown that amphibian defensive skin secretions are a rich source of new functional peptides, making them desirable candidates for the creation of innovative drugs.

In this thesis, a novel antimicrobial peptide, named QUB-1942, was isolated and identified from the skin secretions of Phyllomedusa hypochondrialis, and via "shotgun" molecular cloning, the biosynthetic precursor sequence of QUB-1942 was obtained. Afterwards, RP-HPLC, MALDI-TOF-MS and MS/MS fragmentation sequencing were employed to double confirm the structure of this novel peptide. The mature peptide was synthesised via solid phase peptide synthesis and subjected to minimal inhibitory concentration (MIC) assays using different micro-organisms and haemolytic activity assays using horse red blood cells where the maximum test concentration used was 256 µM. The results obtained from three individual experiments showed that QUB-1942 had no significant broad-spectrum antibacterial activity against, S. aureus, E. coli and Candida albicans. Meanwhile, the MTT assay showed that QUB-1942 also had no significant anti-prolifertive activity against these three microorganisms.

Thesis is embargoed until 31st December 2029.

Date of Award	Dec 2024
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Lei Wang (Supervisor), Chengbang Ma (Supervisor) & Tianbao Chen (Supervisor)