The Discovery and Functional Evaluation of a Novel Bioactive Peptide, QUB-3411, from the Frog Skin Secretion of Hylarana guentheri

  • Xinyi Chen

Student thesis: Masters ThesisMasters

Abstract

Skin secretions of amphibians are abundant resources for bioactive compounds which have been reported to have multiple functions, like proteins, peptides, steroids, alkaloids and biogenic amines. Bioactive peptides, especially the antimicrobial peptides (AMPs) are considered to be promising clinical drug candidates as they are highly effective in defending against various pathogens and difficult for pathogens to grow drug resistance.
In this study, a novel peptide QUB-3411 precursor encoding cDNA was obtained from the frog skin secretions of Hylarana guentheri by using ‘shotgun’ cloning. The amino acid sequence was translated and the mature peptide was speculated by comparison with formally reported peptides in NCBI database. It showed strong similarity with antimicrobial Brevinin-2 family peptides. QUB-3411 was synthesised by solid-phase peptide synthesis (SPPS) and its functions were tested. The results indicated that QUB-3411 had high anti-microorganism potency against the Gram-negative bacterium, Escherichia coli (E. coli), the Gram-positive bacterium, Staphylococcus aureus (S. aureus) and the fungus, Candida albicans (C. albicans) with minimum inhibitory concentrations (MIC) of 2 µM. QUB-3411 showed better potency against human non-small cell lung cancer cell line (NCI-H157) than the human glioblastoma cell line (U251MG) and the human prostate cancer cell line (PC-3) with half inhibitory concentrations of 2.702 µM, 11.01 µM and 8.739 µM respectively, indicating selective antiproliferative activity. Besides, QUB-3411 showed relatively low haemolysis activity against horse erythrocytes but the therapeutic window was narrow. The discovery of the novel peptide QUB-3411 is a complementary of peptide research and further studies are needed to develop it as a pharmacological candidate. This study will aid further researches related to the discovery and functional evaluation of peptides from frog skin secretions.
Date of Award29 Aug 2018
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SupervisorMei Zhou (Supervisor), Lei Wang (Supervisor) & Tianbao Chen (Supervisor)

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