Discovery, bioactivity evaluation and rational design of natural-occurring peptides from Agalychnis annae and Rana tagoi okiensis

There are multiple biofunctional peptides in amphibians which assist in their survival in diverse environments. Many bioactive peptides from this source were found to have the potential to be developed into new drugs in the future. In this thesis, two peptides found in frogs and their analogues exhibited various bioactivities, namely, antimicrobial, anticancer, myotropic activity upon smooth muscle and so on.<br/><br/>A novel bioactive peptide, QUB-2849, was first identified from the skin secretions of the blue-sided leaf frog, Agalychnis annae, by use of molecular cloning. It was found to be equipped with antimicrobial, anticancer and low haemolytic activity. Targeting the truncation of the N terminus of the original dermaseptin peptide, QUB-1875, QUB-1642 and QUB-1159 were designed and synthesized. The truncation could maintain the antimicrobial activity and weaken the haemolysis. Then, analogues, QUB-1159, QUB-2132 and QUB-2683 were designed and their anticancer activity was assessed as compared with that of QUB-2849.This was to ascertain if there was a possibility to develop an excellent anticancer peptide by using a fusion membrane-lytic peptide with a typical sequence of the C-terminus of a dermaseptin peptide or a known anticancer peptide fragment PMI, targeting p53 site. Only natural peptide, QUB-2849, had selective anticancer activity and its anticancer mechanism against the prostate cancer cell line, PC-3, was found to be membrane lysis. <br/><br/>Another peptide, DK22, from the brain of Oki Tago's brown frog, Rana tagoi okiensis, and its truncated form, QUB-1228.5, with the middle disulphide bonds and their respective non-oxidized analogues, QUB-2490 and QUB-1230.5, were studied to explore their bioactive functions. These peptides showed varying degrees of myotropic effects on rat bladder smooth muscle relaxation which might be related to potassium ion channels. QUB-1230.5 and QUB-2490 could influence inflammatory cytokine production in rat macrophages, which might be related to their antioxidant activity. <br/> <i><br/>Thesis embargoed until 31 December 2026</i>.<br/>

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2021

Author dc:creator

• Ji, Ying

Advisors dc:contributor.advisor

• Wang, Lei
• Chen, Tianbao
• Zhou, Mei

• Antimicrobial peptide
• anticancer peptide
• myotropic activity
• anti-inflammation
• dermaseptin

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/ccf96aaf-cc39-4686-9889-28df186d8392

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/ccf96aaf-cc39-4686-9889-28df186d8392