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oai:figshare.com:article/32641209 2026-10-01T16:25:00Z portal_1172 item_type_8 month_year_10_2026

Identification, optimisation, and structure-activity relationship study of Caerin 1 peptides from the frog skin secretion of Litoria caerulea Zhengze Sun (14716112) PUREID: 640716609 Antimicrobial peptides selectivity hinge structure Caerin 1 membrane-active peptides The golden ear of antibiotic has passed for decades, the current marketed antimicrobial agents are losing their ability to combat the increasingly resistant ‘superbugs’ with multidrug resistance. Amphibian skin secretions are a natural resource rich in bioactive compounds, and the antimicrobial peptides in these secretions are believed to have significant potential for combating antimicrobial resistance. In this study, a novel antimicrobial peptide was identified from the skin secretion constructed cDNA library precursor named Caerin 1.1-LC. Antimicrobial peptide Caerin 1.1-LC had a certain antimicrobial activity and anticancer activity through series biological activity evaluation. However, the cytotoxicity of Caerin 1.1-LC is not acceptable for clinical requirement. Hence, in chapter 3, the helix structure was modified in order to optimize the antimicrobial activity and reduce the cytotoxicity. The result indicates that the positive charge improvement on helix structure improve the antimicrobial activity and also influence the cytotoxicity. There are limitations to selective alteration by modifying the hinge motif. The hinge structure is unique structure in Caerin 1 family, the previous study has proved the important influence on antimicrobial activity. In chapter 4, the modification strategy focus on the hinge structure to optimize the antimicrobial activity and cytotoxicity. The result indicates that the hydrophobicity of hinge motif dramatically influence cytotoxicity, Hence, Caerin 1.1-LC V(D)V(D) with D-form amino acid substitution on hinge motif greatly increased selectivity which indicates the modification strategy improve the selectivity of Caerin 1.1-LC to meet the clinical treatment requirement. Due to the lack of general applicability of the independent sample modification strategy success, other samples were selected for hinge structure modification in chapter 5 to eliminate the contingency of modification strategy. Caerin 1.11 which was discovered from previous researcher study was optimized through hinge structure D-form amino acids substitution. After serial biological activity screens, Caerin 1.11 V(D)V(D) was identified as the acceptable antimicrobial agents with ideal antimicrobial activity and low cytotoxicity. Caerin 1.11 V(D)V(D) meet the initial clinical requirement as antibiotic candidates and proved the feasibility of modification strategy of Caerin 1 family peptide for selectivity enhancement. The classical alpha helical structure AMPs has a low selectivity due to the membrane disruption mechanism. AMPs have to overcome the selectivity problem to meet the clinical treatment requirement. In this thesis, the discovery of the novel antimicrobial peptide Caerin 1.1-LC from frog skin secretion and explore the modification strategy for better selectivity indicate further direction for the antimicrobial agents development. The unnatural amino acids substitution strategy on hinge structure has great improvement on the selectivity of Caeirn 1 family peptide and the modification provide a universal optimization strategy for antimicrobial peptides. The exploration of the optimization strategy may contribute to the development of antibiotic candidates and the reduction of the probability of bacterial resistance.<br><br><i>Thesis is embargoed until 31 July 2030</i>. 2026-10-01T16:25:00Z Text Thesis 10.17034/32641209.v1 https://figshare.com/articles/thesis/Identification_optimisation_and_structure-activity_relationship_study_of_Caerin_1_peptides_from_the_frog_skin_secretion_of_Litoria_caerulea/32641209 All Rights Reserved Open Access after 2030-07-31