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

Erik Strandberg; Deniz Tiltak; Marco Ieronimo; Nathalie Kanithasen; Parvesh Wadhwani; Anne S. Ulrich

doi:10.1351/pac200779040717

Publicly Available Published by De Gruyter January 1, 2009

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

Erik Strandberg , Deniz Tiltak , Marco Ieronimo , Nathalie Kanithasen , Parvesh Wadhwani and Anne S. Ulrich

From the journal Pure and Applied Chemistry

https://doi.org/10.1351/pac200779040717

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.

Keywords: amphipathic peptides; antimicrobial peptides; biological assays; cationic α-helices; C-terminal modifications; designed peptide antibiotics

Conference

International Symposium on Chemistry of Natural Products (ISCNP-25) and 5th International Conference on Biodiversity (ICOB-5), International Conference on Biodiversity, International Symposium on the Chemistry of Natural Products, ICOB, ISCNP, Biodiversity, Natural Products, 25th, Kyoto, Japan, 2006-07-23–2006-07-28

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Published Online: 2009-01-01

Published in Print: 2007-01-01

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

Abstract

Conference

References

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