Structure-Activity Relationship, Conformational and Biological Studies of Temporin L Analogues

Temporins are naturally occurring peptides with promising features, which could lead to the development of new drugs. Temporin-ITI (TL) is the strongest antimicrobial peptide, but it is toxic on human erythrocytes and this fact makes the design of synthetic analogues with a higher therapeutic index vital. We studied the structure activity relationships of a library of TL derivatives focusing on the correlation between the a-helix content of the peptides, the nature of their cationic residues, and their antibacterial/antiyeast/hemolytic activities. We found that the percentage of helicity of TL analogues is directly correlated to their hemolytic activity but not to their antimicrobial activity. In addition, we found that the nature of positively charged residues can affect the biological properties of TL without changing the peptide's helicity. It is noteworthy that a single amino acid substitution can prevent the antimicrobial activity of TL, making it a lytic peptide presumably due to its self-association. Last,, we identified a novel analogue with properties that make it an attractive topic for future research.