Identification and functional study of a bioactive peptide QUB-2007 from the skin secretion of the bicolour tree-frog Phyllomedusa bicolor

Abstract

Antimicrobial peptides secreted in amphibian skin secretions have many important bioactivities and act as the first line of defence against invading microorganisms. In this thesis, QUB-2007, a peptide belonging to the Phylloseptin family of the Dermaseptin superfamily, was derived from the skin secretion of Phyllomedusa bicolor. The peptide sequence was obtained by molecular cloning through constructing a cDNA library with isolated mRNA from frog skin secretion. The peptide was synthesised by solid phase peptide synthesis, purified using reversed-phase high performance liquid chromatography and structurally-confirmed by MALDI-TOF MS. In broth microdilution assays, QUB-2007 showed antimicrobial activities against the Gram-negative bacterium, Escherichia coli (E. coli ATCC CRM 8739), and the yeast, Candida albicans (C. albicans ATCC CRM 10231) at concentration of 32 μM, and the Gram-positive bacterium, Staphylococcus aureus (S. aureus ATCC CRM6538) at a concentration of 8 μM. In terms of MTT anticancer cell proliferation assays, QUB-2007 was shown to have anticancer activities against HCI-H838 lung cancer cells at a concentration of 10-4 M. With regard to haemolysis, QUB-2007 was haemolytic at concentrations of 32 μM could be 15%.

In conclusion, QUB-2007 has potential to be a drug, but its haemolytic activity is a big obstacle. It can be achieved by modifying the peptide, such as in changing certain amino acid sequences to change its cationicity, hydrophobicity and amphipathicity.

Thesis embargoed until 31 December 2026.

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