Discovery and design of novel bioactive peptides from amphibian skin secretion

Abstract

In this thesis, molecular cloning techniques were used to obtain the sequences of natural antimicrobial peptides and their synthesis was achieved using solid-phase synthesis (SPPS). In addition, the peptides were purified and identified by high-performance liquid chromatography (HPLC) and MALDI-TOF MS, and their biological activity was determined.

In the third chapter, a natural active peptide, QUB-1369, was identified and isolated from Amolops hainanensis, and it was found to be more effective against the Gram-positive bacterium, S. aureus, and less effective against the Gram-negative bacterium, E.coli and yeast, in a series of functional assays. This peptide was structurally-modified and it was found that the antimicrobial spectrum of the analogue, QUB-1464, was expanded to a certain extent, and the antimicrobial function was significantly improved. In addition, there was an inevitable decrease in haemolytic activity. Therefore, the rational design modification of this AMP helped to improve its therapeutic activity.

In Chapter 4, an antimicrobial peptide was identified in Agalychnis callidryas with a known sequence, and because it contained a specific sequence, it was necessary to investigate the relationship between its structure and function. Firstly, changing the size of the side chain groups of its amino acid residues had a large effect on the activity. Secondly, the balance between the hydrophobicity and the number of charges also had a powerful influence on the cytotoxicity as well as on the activity.

In the study in Chapter 5, the idea of a modified hybrid peptide (chimaera) was presented. The N terminus of different families of AMPs was selected for fusion with the fixed C terminus, and the changes in functional activity and toxicity were observed to identify the hybrid peptides with a relatively high therapeutic potential. The results showed that this modification idea played a very positive role in future studies of AMPs.

Thesis embargoed until 31 December 2026.

Date of Award	Dec 2021
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Lei Wang (Supervisor), Tianbao Chen (Supervisor), Mei Zhou (Supervisor) & Xinping Xi (Supervisor)