An adamantyl amino acid containing gramicidin S analogue with broad spectrum antibacterial activity and reduced hemolytic activity.
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.
Kapoerchan
Varsha V
VV
Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Knijnenburg
Annemiek D
AD
Niamat
Miquel
M
Spalburg
Emile
E
de Neeling
Albert J
AJ
Nibbering
Peter H
PH
Mars-Groenendijk
Roos H
RH
Noort
Daan
D
Otero
José M
JM
Llamas-Saiz
Antonio L
AL
van Raaij
Mark J
MJ
van der Marel
Gijs A
GA
Overkleeft
Herman S
HS
Overhand
Mark
M
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
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D010455:Peptides; D006096:Gramicidin; D000218:Adamantane