Characterisation, bioactivity evaluation and rational design of bioactive peptides from <i>Hylarana latouchii</i> skin secretion

In Chapter 4, brevinin-1HL identified in the skin secretion of Hylarana latouchii was evaluated for its biological activity. Five analogues were designed through D-type amino acid substitution and changing the amino acids in the hydrophobic face. It was found that the secondary structure, especially the helicity between these peptides, plays a significant role in their actions.

And the designed analogue, brevinin-1HL-D-9L, was considered as a potential drug candidate with potent antibacterial activity with low haemolysis at its effective values. In Chapter 5, a novel peptide, palustrin-2LTb, identified in the skin secretion of Hylarana latouchii was shown to have good antibacterial activity against selected pathogens. To reduce the manufacturing cost and decrease toxicity, trypsin-cleavage mimicking modification strategy was ultilised to produce predicted fragments.

Seven such truncated derivatives of palustrin-2LTb were synthesised and tested for their biological activities. Functional screening data indicated that truncated fragment 3 not only maintained and optimised antimicrobial efficacy of the parent peptide, but also showed great in vivo therapeutic potential in an MRSA-infected insect larvae model. Due to its strong antibacterial activity, minimal haemolytic activity, and ability to kill MRSA in an in vivo model, fragment 3 showed outstanding effects and had obvious potential to become a new antimicrobial agent. <br><br><i>Thesis is embargoed until 31 July 2028</i>.<br><br><br>