Identification, characterisation and design of bioactive peptides from Chinese frogs

Abstract

Antimicrobial peptides from amphibian skin secretions have become candidates as replacements for conventional antibiotic therapies. Temporin is an AMP type found in skin secretions of frogs from the family Ranidae, In Chapter 3, a novel temporin family peptide, QUB1434, was identified from Pelophelax plancyi fukienensis. it exhibited strong activity against Gram-positive bacteria but no effect on Gram-negative bacteria. A series of analogues were designed using QUB-1434 as a template, to study the structure-activity relationships of the temporins. Incorporation of Cha caused a great improvement in peptide activity against Gram-positive bacteria. TAT sequences with no antibacterial properties and a sequence that targets breast cancer cells, were also been introduced to improve the antibacterial and anticancer activity of the natural peptide. In the next chapter, DMPC-1OA is a lO-mer derivative with a Cha at the C-terminus from a dermaseptin peptide. DMPC-1 OA was found to have broad-spectrum antimicrobial activity against isolates from cystic fibrosis patients but a considerable haemolytic effect. To further improve haemolysis and stability, DMPC-1OB was designed using D-amino acid residues. Through antimicrobial assay, cytotoxicity assay and in vitro and in vivo stability assays, it was found that DMPC-1OB had strong and broad-spectrum antimicrobial activity, low cytotoxicity and high stability in vitro and in vivo. In the last chapter, a 22-mer amidated peptide, named QUB-2395 with an internal disulphide bridge from the skin secretion of Odorrana versabilis, was subjected to the study. Truncated derivatives derived from the loop, were designed to detect the specific location of its active core. QUB-2395 was a class of myotropic peptide producing potent and dose-dependent contraction of the smooth muscle of rat urinary bladder. However, its derivatives were tested and had a weaker myotropic function. However, it was found that QUB-2395 and its derivatives also exhibited in vitro antioxidant activity anti-inflammatory capacity.

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