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Pure Appl. Chem., 2007, Vol. 79, No. 4, pp. 717-728

Influence of C-terminal amidation on the antimicrobial and hemolytic activities of cationic α-helical peptides

Erik Strandberg1, Deniz Tiltak2, Marco Ieronimo2, Nathalie Kanithasen2, Parvesh Wadhwani1 and Anne S. Ulrich1,2

1 Institute for Biological Interfaces, Forschungszentrum Karlsruhe, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
2 Institute of Organic Chemistry, University of Karlsruhe, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany

Abstract: The effect of C-terminal amidation on the antimicrobial and hemolytic activities of antimicrobial peptides was studied using three cationic peptides which form amphiphilic α-helices when bound to membranes. The natural antimicrobial peptide PGLa, the designer-made antibiotic MSI-103, and the cell-penetrating "model amphipathic peptide" (MAP) are all amidated in their original forms, and their biological activities were compared with the same sequences carrying a free C-terminus. It was found that, in general, a free COOH-terminus reduces both the antimicrobial activity and the hemolytic side effects of the peptides. The only exception was observed for MSI-103, whose antimicrobial activity was not decreased in the acid form. Having shown that the therapeutic index (TI) of this novel peptide is significantly higher than for the other tested peptides, with high antibiotic activity and little undesired effects, we suggest that it could be a useful starting point for further development of new peptide antibiotics.