Identification and modification of novel antimicrobial peptides from Agalychnis annae

The analogue produced by hydrophobic modification showed efficacy against drug-resistant cancer cells. Both the parent peptide and the analogue were found to have a dual mechanism of membrane permeabilisation and inducing apoptosis, and also showed a synergistic effect with cisplatin. For peptides QUB-2831 and QUB-2561, by rationally reducing α-helicity, the haemolytic activity and toxicity to normal cells were successfully reduced while retaining most of the antimicrobial activity.

Subsequently, the analogue of QUB-2831 further enhanced its stability in the serum environment through C-terminal amidation. For the analogues of QUB-2561, the antimicrobial activity was restored or even stronger than the parent peptide by gradually increasing the charge. Furthermore, mechanism analysis confirmed that these peptides mainly exert their effects through rapid membrane permeabilisation and depolarisation.<br><br>In summary, these findings indicate that rational structural modification can effectively overcome the limitations of natural AMPs and provide a library of optimized analogues with potential for treating multidrug-resistant bacteria and drug-resistant tumours.<br><br><i>Thesis is embargoed until 31 July 2031</i>.<br>