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An Adamantyl Amino Acid Containing Gramicidin S Analogue with Broad Spectrum Antibacterial Activity and Reduced Hemolytic Activity
Author(s) -
Kapoerchan Varsha V.,
Knijnenburg Annemiek D.,
Niamat Miquel,
Spalburg Emile,
de Neeling Albert J.,
Nibbering Peter H.,
MarsGroenendijk Roos H.,
Noort Daan,
Otero José M.,
LlamasSaiz Antonio L.,
van Raaij Mark J.,
van der Marel Gijs A.,
Overkleeft Herman S.,
Overhand Mark
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201001686
Subject(s) - hemolysis , antibacterial activity , gramicidin s , gramicidin , peptide , antimicrobial , chemistry , bacteria , amphiphile , gram negative bacteria , cationic polymerization , antibiotics , broad spectrum , stereochemistry , combinatorial chemistry , biochemistry , membrane , escherichia coli , biology , organic chemistry , genetics , polymer , copolymer , gene , immunology
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.