Identification of natural antimicrobial peptides from amphibians: structural modification for bioactivity development

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>