Rational design and bioactive evaluation of an antimicrobial peptide, Palustrin-2ISb, from the skin secretion of the frog, Odorrana ishikawae

Palustrin-2 peptides were found to exhibit broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria and have low haemolytic activity. Therefore, GL-29, a truncated form of palustrine-2ISb, was used as a template in this study and in an attempt to investigate its structure-activity relationships and try to find a peptide with higher antimicrobial potency and good selectivity through modification.<br><br>In the third chapter, GL-29 as well as the truncated analogue GL-22, were studied to identify the function of the "Rana box", which was confirmed to have no impact on antimicrobial activity, but the deletion of this motif notably decreased the haemolytic activity and antiproliferative activity both against human cancer cells and normal cells.

In chapter 4, five short truncates of GL-22, including the N-terminal short analogue GL-9 and C-terminal short derivatives LF-10, FV-9, VN-8, FV-8 were designed and they all exhibited nearly no antimicrobial activities. In the fifth chapter, the structure-activity relationships were studied by designing eight short analogues of GL-9, named from GL-9-a to GL-9-h with different characteristics. And the result showed that for the short N-terminal derivatives, higher hydrophobicity was crucial for the antimicrobial activity and the position of the hydrophobic residue is of great importance, however, the improvement of charge was useless for these short compounds.