An Adamantyl Amino Acid Containing Gramicidin S Analogue with Broad Spectrum Antibacterial Activity and Reduced Hemolytic Activity

Kapoerchan, V.V.; Knijnenburg, A.D.; Niamat, M.; Spalburg, E.; Neeling, A.J. de; Nibbering, P.H.; ... ; Overhand, M. (2010)

Article / Letter to editor

The cyclic cationic antimicrobial peptide gramicidin S (GS) is an effective topical antibacterial agent that is toxic for human red blood cells (hemolysis). Herein, we present a series of amphiphilic derivatives of GS with either two or four positive charges and characteristics ranging between very polar and very hydrophobic. Screening of this series of peptide derivatives identified a compound that combines effective antibacterial activity with virtually no toxicity within the same concentration range. This peptide acts against both Gram-negative and Gram-positive bacteria, including several MRSA strains, and represents an interesting lead for the development of a broadly applicable antibiotic.

• amino acids antibiotics gramicidin methicillin-resistant Staphylococcus aureus (MRSA) peptides resistant staphylococcus-aureus beta-sheet structure peptide antibiotics conformational-analysis biomimetic synthesis biological-activity linear precursors cyclic-peptides turn mimetics derivatives

• All authors: Kapoerchan, V.V.; Knijnenburg, A.D.; Niamat, M.; Spalburg, E.; Neeling, A.J. de; Nibbering, P.H.; Mars-Groenendijk, R.H.; Noort, D.; Otero, J.M.; Llamas-Saiz, A.L.; Raaij, M.J. van; Marel, G.A. van der; Overkleeft, H.S.; Overhand, M.
• Date: 2010-12-31
• Journal: Chemistry - A European Journal
• Volume: 16
• Issue: 40
• Pages: 12174 - 12181
• DOI: doi:10.1002/chem.201001686