Identification and bioactivity evaluation of a novel peptide, QUB-2603, from the skin secretion of the black-striped frog, Hylarana nigrovittata

Abstract

Over time, bacteria, viruses, fungi, and parasites progressively acquire resistance to drugs, and the improper use of antibiotics further hastens the development of drug resistance. This has become a worldwide menace for the past decade. With the escalating issue of drug resistance, there is a pressing need to actively pursue the discovery of new antimicrobial compounds. Antimicrobial peptides (AMPs) obtained from the defensive skin secretions of amphibians have exceptional biological properties. Consequently, AMPs are acknowledged as a very promising category of chemicals for possible therapeutic uses.

The precursor peptide of QUB-2603 was discovered in the skin secretion of Hylarana nigrovittata by the process of 'shotgun' cloning. The mature peptide encoded by this precursor was then sequenced as FIGPVLKIATSILPTAICKIFKKC and synthesised using solid phase peptide synthesis. First, employ matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry to analyze and validate the structure of the peptide to ensure a successful synthesis. Then, utilize reversed-phase high performance liquid chromatography (RP-HPLC) to purify the final peptide product. In order to assess the bioactivity of QUB-2603, a variety of experiments were performed, including antimicrobial assays, cell viability assays, and haemolysis assays. The findings demonstrated that QUB-2603 shown antibacterial properties against S. aureus (with a minimum inhibitory concentration of 2µM), E. coli (with a minimum inhibitory concentration of 4µM), and C. albicans (with a minimum inhibitory concentration of 4µM). Additionally, it had good anti-cancer properties(IC50=2.65 μM). However, it also demonstrated significant hemolytic capacity(HC50=23.17 μM).QUB-2603 shows promise as a potential antibacterial medication candidate for further investigation, based on these findings.

Thesis is embargoed until 31 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)