Exploration of the structure-function relationships of two novel antimicrobial peptides from amphibian skin secretion, through rational design and in vitro studies

Abstract

Amphibian skin-derived antimicrobial peptides (AMPs) have been making notable progress in becoming the potential alternative choices to conventional antibiotics. Two novel AMPs, t-DPH1 and B1AW were first isolated from frog skin secretion in this project. A series of bioassays were conducted to evaluate their bioactivities, and the natural AMPs were used as templates to explore the structure-function relationships and optimise their bioactivities.
Through a series of bioassays, the bioactivities of two novel peptides were evaluated. Through rational design, the structure-function relationships of these two peptides were explored. It was proved that the three conserved features of the dermaseptin family were indispensable to the antimicrobial activity of t-DPH1. The cationicity-enhanced analogue, t-DPH1-K was regarded as a potential drug candidate with dual effect and low possibility to induce drug resistance. Also, through peptide modification, the antimicrobial spectrum of B1AW was broadened and the exceeded haemolytic activity was reduced. The findings of this project provide creative insights into the role of natural drug discovery in providing templates for structural modification for activity enhancement and balancement.

Thesis embargoed until 31 July 2027.

Date of Award	Jul 2022
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Mei Zhou (Supervisor), Lei Wang (Supervisor) & Tianbao Chen (Supervisor)