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oai:figshare.com:article/32805752 2026-10-01T16:13:27Z portal_1172 item_type_8 month_year_10_2026

Identification and modification of novel antimicrobial peptides from Agalychnis annae Weichang Li (15211966) PUREID: 688027549 Antimicrobial peptides agalychnis annae dermaseptins structure–activity relationship multidrug resistance Multidrug-resistant (MDR) bacteria and chemotherapy-resistant cancer are becoming serious health issues, and there is an urgent need for novel therapeutic agents. Antimicrobial peptides (AMPs) have gained attention due to their broad-spectrum antimicrobial activity, unique mechanisms of action, and the fact that some of them also possess other activities such as anticancer properties, making them potential solutions to solve these problems. Amphibian skin secretions are the richest natural source of AMPs. In this study, ‘shotgun’ cloning technology was utilized to identify and synthesize three natural AMPs—QUB-3018, QUB-2831, and QUB-2561—from the skin secretions of Agalychnis annae. A series of modified peptides were designed and synthesized through strategies such as sequence truncation, charge modulation, and hydrophobicity adjustment, elucidating the structure-activity relationship and optimizing their therapeutic potential. The natural peptide QUB-3018 was found to possess anticancer activity, but its effect on drug-resistant tumour cells showed reduced efficacy. 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. 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. Thesis is embargoed until 31 July 2031. 2026-10-01T16:13:27Z Text Thesis 10.17034/32805752.v1 https://figshare.com/articles/thesis/Identification_and_modification_of_novel_antimicrobial_peptides_from_Agalychnis_annae/32805752 All Rights Reserved Open Access after 2031-07-31