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Identification of natural antimicrobial peptides from amphibians: structural modification for bioactivity development Weining Yin (3862687) PUREID: 588605509 Antimicrobial peptide anti-cancer peptide Phylloseptin The vastness of nature has been the source of medicine for humanity since ancient times, and the diversity of natural products brings continuous inspiration for drug research and development. This study targeted antimicrobial peptides (AMPs) in the skin secretions of frogs from the Phyllomedusa genus, to explore their activities, functions, and the effects of structure on activities of component AMPs and to provide high-quality candidates for more far-reaching drug development. In Chapter 3, PSTO2 showed excellent bacteriostatic activity and sterilization function under multiple antibacterial experiments, with high bactericidal speed and efficiency. In addition, PSTO2 also exhibited significant cancer cell inhibitory activity and could harm tumour cells through various mechanisms, including damage to cell membranes and induction of apoptosis. Moreover, in safety and toxicity tests, PSTO2 showed relatively low toxicity in vivo and in vitro. Therefore, PSTO2 has been proven to be an effective AMP with multiple functions and high safety, which has good potential for bacterial control and cancer drug development. In Chapter 4, eight analogues of PSTO2 were designed according to different structural characteristics and amino acid compositions, and their antibacterial, anti-biofilm, and anti-cancer activities were tested. According to the results, SRD7 had the highest comprehensive therapeutic index, has a particularly outstanding therapeutic effect and killing rate against Gram-positive bacteria, and can significantly destroy cell membranes. It thus has a significant impact on overcoming drug resistance. Also, this peptide showed higher salt ion and serum stability and safety, making it an excellent candidate for development as an alternative antibiotic agent. In Chapter 5, eight analogues were designed based on DSH2, an existing AMP derived from the skin secretions of another frog from the Phyllomedusa genus (Phyllomedusa hypochondria). Among the modified analogues, DW exhibited the most prominent therapeutic index, with intense antibacterial and anticancer activity as well as low toxicity. Therefore, increasing the hydrophobic and hydrophilic amino acid distribution of DSH2 enhanced its antibacterial and anticancer effects. Due to its efficacy in treating ESKAPE biofilm infections, and various high-risk cancer cells, DW has the potential to become a novel antibacterial and anticancer drug lead. <br><i><br>Thesis is embargoed until 31 July 2029.</i> 2026-10-01T16:39:12Z Text Thesis 10.17034/32639547.v1 https://figshare.com/articles/thesis/Identification_of_natural_antimicrobial_peptides_from_amphibians_structural_modification_for_bioactivity_development/32639547 All Rights Reserved Open Access after 2029-07-31