Tuning hydrophobicity of highly cationic tetradecameric Gramicidin S analogues using adamantane amino acids.
Ring extended Gramicidin S analogues containing adamantane amino acids and six cationic residues were designed and evaluated. Systematic replacement of the hydrophobic residues with adamantane amino acids resulted in a small set of compounds with varying amphipathic character. It was found that the amphipathicity of these compounds is correlated to their biological activity. Several bacterial strains including MRSA strains were shown to be killed by the novel peptides. The most potent antibacterial peptides are tetradecameric GS analogues containing six positives charges and two adamantane moieties.
Leiden Institute of Chemistry, Leiden University, The Netherlands.
Annemiek D
AD
Knijnenburg
Varsha V
VV
Kapoerchan
Emile
E
Spalburg
Albert J
AJ
de Neeling
Roos H
RH
Mars-Groenendijk
Daan
D
Noort
Gijs A
GA
van der Marel
Herman S
HS
Overkleeft
Mark
M
Overhand
D000218:Adamantane / Q000737:chemistry*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D002412:Cations / Q000737:chemistry; D002942:Circular Dichroism; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects
D000596:Amino Acids; D000890:Anti-Infective Agents; D002412:Cations; D006096:Gramicidin; D000218:Adamantane