Bioactive peptides from the skin secretion of Kassina senegalensis

Bioactive peptides in amphibian skin have been reported to have various pharmacological activities. The discoveries of these peptides have become hot spots in the development of new drugs.<br/><br/>In Chapter 3, peptides QUB-1641, QUB-1746, Kassinakinin S and Senegalin were isolated from Kassina senegalensis by molecular cloning. After these peptides were chemically synthesized, they were tested for activities. They were summarized as low-toxic peptides with weak antibacterial activity and no anticancer activity. Only the peptide Kassinakinin S exhibited anti-inflammatory activity.<br/><br/>In Chapter 4, QUB-1641 was modified to optimize its antibacterial effect. The "glycine lysine" motif was applied to replace the amino acids of QUB-1641 to synthesize analogues. By comparing the antibacterial effects of QUB-1641 and its analogues, their structure-activity relationship was studied. When the "glycine-lysine" motif substituted the 8th and 9th amino acids of QUB-1641, the antibacterial efficiency of the peptide was most obviously improved by the increase of the cationic and helix content.<br/>In Chapter 5, the pharmacological activities of QUB-1641, QUB-1746, Kassinakinin S and Senegalin on rat smooth muscle were tested. Among them, QUB-1641 and QUB-1746 induced rat bladder smooth muscle relaxation and their mechanism was closely related to potassium channels. Afterwards, to enhance the effect of QUB-1641 and QUB-1746 on smooth muscle, their sequences were linked with bradykinin (BK) to synthesize fusion peptides QUB-1641BK and QUB-1746BK. QUB-1641BK and QUB-1746BK contracted smooth muscle of rat bladder and ileum. These two fusion peptides also significantly inhibited BK's contraction of rat bladder smooth muscle and could be classified as BK antagonists.<br/><br/>In brief, the activities of four peptides in Kassina senegalensis were screened. These peptides were then optimized to achieve better efficacy. The discovery of these multifunctional peptides will help enrich their therapeutic applications. In addition, the research provides new ideas for the amino acid modification of natural short peptides.<br/><br/><i>Thesis embargoed until 31 December 2026</i>.

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

• Lu, Yueyang

Advisors dc:contributor.advisor

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

• Antimicrobial peptides (AMPs)
• amphibian skin secretion
• motif
• smooth muscle
• antimicrobial activity

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/5e76da40-54f2-48e3-8762-cb39c6d06e41

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/5e76da40-54f2-48e3-8762-cb39c6d06e41