Discovery of bioactive peptides from amphibian skin secretion

Abstract

During the long evolutionary process, amphibians have developed their unique defence mechanisms. Among these, bioactive peptides in special skin secretions produced by frogs have been considered to be one of the rich natural sources for developing new drugs in the future.

In this thesis, several bioactive peptides were identified from the skin secretions of frogs by using RP-HPLC and molecular cloning. Then these peptides were synthesised by solid phase peptide synthesis (SPPS) for researching their biological functions.

In Chapter 3, a novel peptide, phylloseptin-PV1, was discovered and identified from the defensive skin secretion of the White-lined leaf frog, Phyllomedusa vaillantii. It was found not only to demonstrate potent antimicrobial activity against planktonic ESKAPE strains and the yeast, C. albicans, but also inhibited and eradicated the biofilm of S. aureus and MRSA. Therefore, a mice model was used for evaluating its further in vivo antimicrobial activity.

In Chapter 4, a novel dermaseptin peptide, QUB-2522, was identified from the defensive skin secretion of the Northern orange-legged leaf frog, Phyllomedusa hypochondrialis. It exhibited antimicrobial activity against the bacteria, S. aureus and E. coli, at 32 μM concentration, and this activity was not affected by temperatures below 100℃. In order to improve its antimicrobial activity, three analogue peptides, QUB-2534, QUB-2648 and QUB-2574, were modified according to the sequence of QUB-2522 and studied in addition.

In Chapter 5, Frenatin 1.1 and Frenatin 3 from the skin secretion of the Australasian giant white-lipped tree frog, Litoria infrafrenata, and Caeridin-1 from the Australian White’s tree frog, Litoria caerulea, and the designed analogue of this, QUB-1128, were studied for a range of bioactivities. These four peptides showed varying degrees of effect on rat smooth muscle.

Date of Award	Dec 2020
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Mei Zhou (Supervisor), Lei Wang (Supervisor), Chengbang Ma (Supervisor) & Tianbao Chen (Supervisor)