Identification and evaluation of bioactive peptides from amphibian skin and rational design of new analogues

  • Zijian Gong

Student thesis: Doctoral ThesisDoctor of Philosophy


Human demand for novel antimicrobials has increased due to the rapid development of antibiotic-resistant bacteria. Because of their remarkable antimicrobial capacity, antimicrobial peptides are at the forefront of new antibacterial drugs. In our research, we are working with the isolation and identification of small molecule peptides with potent bioactivity from frog skin secretions and performing functional experiments on them. In chapter 3, DRP-AC4, a novel dermaseptin family peptide was isolated and identified. DRP-AC4 possesses broad-spectrum antimicrobial activity and inhibits the proliferation of a wide range of cancer cells. In chapter 4, another novel peptide named Temporin-LTd was identified. Temporin-LTd is a linear cationic short alpha-helical peptide with strong antimicrobial activity against Gram-positive bacteria but weak activity against Gram-negative bacteria. In chapter 5, three analogues of DRP-AC4 were designed to employ the influence of cationicity, hydrophobicity and C-terminal amidation on bioactivity. Extended hydrophobic face exhibited higher haemolytic activity and anti-proliferative activity. cationicity-enhanced analogue exhibited higer antimicrobial activity without increasing haemolytic activity.finally, C-terminal amidation removed analogue lost most of its activity. In chapter 6, eight derivatives of Temporin-LTd template were designed and compared their helical content regarding their biological activity. The helical content of Temporin-LTd analogues is associated with their haemolytic and anti-cancer cell proliferative activity, but not associated with their antibacterial activity. Furthermore, we found that the cationic residue type could affect the activity and helical content of Temporin-LTd. Surprisingly, our addition of leucine over glycine at position 9 resulted in the loss of the antimicrobial activity of Temporin-LTd. Finally, we found that disruption of the C-terminal helical structure provides initial thoughts for the development of novel anti-fungal drugs.
Date of AwardJul 2021
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SupervisorMei Zhou (Supervisor), Xiaoling Chen (Supervisor), Tianbao Chen (Supervisor) & Lei Wang (Supervisor)


  • Antimicrobial peptides
  • dermaseptin peptide family
  • tempirin peptide family
  • drug resistance
  • biofilm
  • anti-proliferative

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