The discovery, rational design, and bioactivity evaluation of antimicrobial peptides from the skin secretions of amphibians

Abstract

Antimicrobial peptides from natural organisms have been extensively studied in recent years. Their clinical potential is getting stronger as more new peptides are discovered and modified peptides are designed. A large proportion of antimicrobial peptides have now entered clinical trials. In Chapter 3, BLP-7S and Bombinin-H2L were extracted from the skin secretions of Bombina variegata. They both have good antimicrobial activity, but Bombinin-H2L is less biologically safe and has potential for continued modification. In Chapter 4, a series of analogues were designed on the basis of Bombinin-H2L. Their main activity and toxicity were affected by hydrophobicity, which significantly increased their safety when hydrophobicity was reduced to the safety threshold. When hydrophobicity is reduced to a safe level, increasing the positive charge significantly improves the antimicrobial activity without increasing haemolysis. The best results were obtained with BH2L-8R15R and BH2L-78K, a modified peptide with multiple bactericidal mechanisms. In Chapter 5, to investigate the impact of different living habits on the activity of antimicrobial peptides secreted by frogs, a specific species of tree frog was selected as the research subject. QUB-2048 extracted from the skin secretion of Phyllomedusa hypochondrialis azurea, was modified. This is an antimicrobial peptide of similar length to Bombinin-H2L. The effect of the common modified peptide residues “-PRW-” on the biological activity and spatial structure of this peptide was explored. This will lay the foundation for the rational design of similar peptides of the same family in the future. 

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) & Tianbao Chen (Supervisor)