Synthesis and Evaluation of Structure-Activity Relationship of Pseudopeptide Analogs Corresponding to the Cationic α-Helical Peptides:

초록

Replacement of backbone amide bonds by isosteric units stabilizes biologically active peptides towards enzymatic degradation and may also alter other pharmacokinetic properties in a favorable manner. In addition, incorporation of amide bond isosteres is a convenient way to elucidate the role of selected amide bonds in receptor binding, biological activity and their influence on the secondary structure of peptides. In this regard, replacement of backbone amide bond to corresponding ester bond is well known strategy to investigate the main chain hydrogen bonding and its effect on secondary structure change. We choose the alpha-helical Lysine and Leucine rich cationic antibacterial peptide as a model system. To investigate the role of backbone amide bond and its effect on structure activity, 1 and 7 position amide bond was replaced by ester bond. The effect of the ester bond substitution on the biological activity, binding of the pseudopeptides to the different vesicles, hemolytic activity and secondary structure of these peptides was investigated.