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An Adamantyl Amino Acid Containing Gramicidin S Analogue with Broad Spectrum Antibacterial Activity and Reduced Hemolytic Activity |
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| Authors: | Dr. Varsha V. Kapoerchan Dr. Annemiek D. Knijnenburg Miquel Niamat Emile Spalburg Dr. Albert J. de Neeling Dr. Peter H. Nibbering Roos H. Mars‐Groenendijk Dr. Daan Noort José M. Otero Dr. Antonio L. Llamas‐Saiz Dr. Mark J. van Raaij Prof. Dr. Gijs A. van der Marel Prof. Dr. Herman S. Overkleeft Dr. Mark Overhand |
| Affiliation: | 1. Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden (The Netherlands), Fax: (+31)?71‐527‐4307;2. Laboratory for Infectious Diseases, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven (The Netherlands);3. Department of Infectious Diseases, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden (The Netherlands);4. Defense, Security and Safety, TNO, P.O. Box 45, 2280 AA Rijswijk (The Netherlands);5. Departamento de Bioquímica y Biología Molecular, Faculta de Farmacia, Campus Sur, Universidad de Santiago de Compostela, 15782 Santiago de Compostela (Spain);6. Unidad de Rayos X (RIAIDT), Laboratorio Integral de dinámica y Estructura de Biomoléculas “José R. Carracido”, Edificio CACTUS, Campus Sur, Universidad de Santiago de Compostela, 15782 Santiago de Compostela (Spain);7. Departamento de Biología Estructural, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Baldiri Reixac 10, 08028 Barcelona (Spain) |
| Abstract: | 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. |
| Keywords: | amino acids antibiotics gramicidin methicillin‐resistant Staphylococcus aureus (MRSA) peptides |