Date Published: , 2011
Publisher: A.I. Gordeyev
Author(s): O.V. Samsonova, K.S. Kudryashova, A.V. Feofanov.
The antimicrobial peptide Ltc1-K and its derivates without one, two, then three N-terminal amino acid residues were studied based on the hypothesis (backed by some experimental data) that the hydrophobic N-terminal moiety of linear cationic antimicrobial peptides defines their haemolytic activity. It was discovered that the excision of three N-terminal amino acid residues considerably decreases the peptide’s toxicity for eukaryotic cells and simultaneously increases the selectivity of antibacterial activity for some bacteria species. Studies performed with the model membrane systems and human erythrocytes revealed that the main reason for the observed effect is a multifold decrease in the peptide’s affinity to an eukaryotic cellular membrane enriched with zwitterionic phospholipids.
Antimicrobial peptides (AMP) are natural substances that vary in structure and biological functions. They possess in common the capability of inhibiting the vital activity of pathogenic microorganisms. Endogenic AMPs are considered to be one of the key factors (and simultaneously an evolutionarily ancient one) of the innate immunity of multicellular organisms, which enables them to be regarded as prototypes for a new generation of antibiotics [1–3]. The search for new AMPs and the detailed study of the existing ones is stimulated by the development of resistance to conventional antibiotics in microorganisms and by the capability of many AMPs to overcome this resistance.
Biological activities of peptides
The excision of three N-terminal amino acid residues in Ltc1-К considerably reduces the haemolytic activity of AMPs, thus increasing the selectivity of its antibacterial action.