Discovery and functional evaluation of a novel peptide, QUB-3034, from the skin secretion of Phyllomedusa sauvagei

Abstract

Antimicrobial resistance is a growing global health problem, and finding alternatives to traditional antibiotics is becoming more urgent. Antimicrobial peptides, or AMPs, are a promising solution because they have broad-spectrum activity and can target bacteria even cancer cells. Dermaseptins (DRS) are a family of peptides widely found in the skin secretions of tree frogs. Their molecular characteristics are that they are rich in basic amino acid residues and tend to form α-helical secondary structures in hydrophobic environments. Existing studies classify DRS as antimicrobial peptides based on in vitro experiments that have confirmed that they have broad-spectrum inhibitory activity and eukaryotic pathogens while also exhibiting significant immunomodulatory functions.

In this study, a bioactive peptide, QUB-3034, was discovered from skin secretion of Phyllomedusa sauvagei by shotgun cloning of a novel biosynthetic precursor encoded cDNA smoothly. Through the bioinformatic analysis, the amino-acid sequences of mature peptide was determined as GLRSKIWLWVLLMLWQESNKFKKM. After synthesised by the method of solid phase peptide synthesis, RP-HPLC and LCQ-MS were subjected to the detection and purification of QUB-3034. The lyophilised pure peptide replicates were subjected to different assays and examinations were operated to evaluate different aspects of bioactivity of QUB-3034. Experiments have shown that it has no killing ability against Gram-negative bacteria, Gram-positive bacteria, and fungi. At the same time, QUB-3034 has no obvious killing ability against human non-small cell lung cancer H838 cells. However, its haemolytic toxicity and toxicity to normal human cells are very weak. Therefore, in the future, by changing certain amino acids in the peptide chain, it is hoped that its antibacterial and anti-cancer abilities can be improved while maintaining low toxicity.

Thesis is embargoed until 31 December 2030.

Date of Award	Dec 2025
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Tianbao Chen (Supervisor), Mei Zhou (Supervisor) & Lei Wang (Supervisor)