title: An adamantyl amino acid containing gramicidin S analogue with broad spectrum antibacterial activity and reduced hemolytic activity.
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.
authors.affiliation: Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Varsha V
authors.initials: VV
authors.lastname: Kapoerchan
authors.forename: Annemiek D
authors.initials: AD
authors.lastname: Knijnenburg
authors.forename: Miquel
authors.initials: M
authors.lastname: Niamat
authors.forename: Emile
authors.initials: E
authors.lastname: Spalburg
authors.forename: Albert J
authors.initials: AJ
authors.lastname: de Neeling
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nibbering
authors.forename: Roos H
authors.initials: RH
authors.lastname: Mars-Groenendijk
authors.forename: Daan
authors.initials: D
authors.lastname: Noort
authors.forename: José M
authors.initials: JM
authors.lastname: Otero
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Llamas-Saiz
authors.forename: Mark J
authors.initials: MJ
authors.lastname: van Raaij
authors.forename: Gijs A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.forename: Mark
authors.initials: M
authors.lastname: Overhand
mesh_terms: D000218:Adamantane / Q000737:chemistry* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000596:Amino Acids; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006096:Gramicidin / Q000737:chemistry* / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D010539:Permeability; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D010455:Peptides; D006096:Gramicidin; D000218:Adamantane