Exploration of the structure-function relationships of two novel peptides from amphibian skin secretion, through rational design and in vitro studies

Here, F-Kas-4 was found to possess similar antimicrobial activities but better antibiofilm activity towards MRSA 12493. These discoveries provided both novel and useful new understanding of how natural medicines are discovered.<br><br>The second novel peptide, Kas-2, was identified from the skin secretion of the African hyperoliid frog, Kassina maculata. Studies showed that Kas-2 had potent bactericidal effects on Gram-positive bacteria and anti-proliferation activity on tested cancer cells.

After the modifications were performed in Chapter 5 and Chapter 6, the results showed that charge enhancement was effective in Kas-2 design. Besides, the first helix was ineffective in the sequence when interacting with bacterial cell membranes. Four designed cell-penetrating peptides with a special motif with tryptophan and arginine residues, displayed potent antimicrobial and anticancer activities but high haemolysis.

These data may provide some ideas to improve the bioactivities of AMPs from Kassina species in further studies.<br><br>Under the studies on the identification and bioactivity evaluation of this two novel peptides Kas-4 and Kas-2, from the skin secretion of two different African frogs, Kassina senegalensis and Kassina maculate, respectively, we found that the positions of two prolines had a great influence on the bioactivities of peptides from Kassina species rather than cationicity and hydrophobicity.

Also, through rational design, activities and haemolysis of Kas-4 and Kas-2 were well improved. This study provided a fresh perspective on the creation of antimicrobial derivatives. <br><br><i>Thesis is embargoed until 31 July 2028.<br></i><br>