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

作者：Kapoerchan Varsha V; Knijnenburg Annemiek D; Niamat Miquel; Spalburg Emile; de Neeling Albert J; Nibbering Peter H; Mars Groenendijk Roos H; Noort Daan; Otero Jose M; Llamas Saiz Antonio L; van Raaij Mark J; van der Marel Gijs A; Overkleeft Herman S; Overhand Mark^*

来源：Chemistry - A European Journal, 2010, 16(40): 12174-12181.

DOI：10.1002/chem.201001686

• amino acids
• antibiotics
• gramicidin
• methicillin-resistant Staphylococcus aureus (MRSA)
• peptides

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.

• 出版日期2010