Melectin MAPs: the influence of dendrimerization on antimicrobial and hemolytic activity.
The recently described antimicrobial peptide melectin (MEP, GFLSILKKVLPKVMAHMK-NH2) exhibits high antimicrobial activity against Gram-positive and Gram-negative bacteria. Here we describe the synthesis and biological activities of 23 new analogues of MEP. We studied the influence of dimerization and tetramerization (MAP-constructs of MEP) on the antimicrobial and hemolytic activities, as well as the role of Met in positions 14 and 17 of the peptide chain. Oxidation of the Met to Met(O) and Met(O2) decreases antimicrobial activity of all tested bacteria if the peptide is in the monomeric form, however, only to Staphylococcus aureus if in the form of dimer or tetramer. Dimerization and tetramerization increase the undesirable hemolytic activity of the peptides. Interestingly, substitution of Leu for Val in position 6 leads to the decrease of hemolytic activity. Introduction of the isosteric amino acid Nle into positions 14 or 17 or both leads to slight increase of hemolytic activity under preservation of high antimicrobial activities. Unfortunately, dimerization again leads to an increase of hemolytic activity.
Niederhafner
Petr
P
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
Bednárová
Lucie
L
Buděšínský
Miloš
M
Safařík
Martin
M
Ehala
Sille
S
Ježek
Jan
J
Borovičková
Lenka
L
Fučík
Vladimír
V
Ceřovský
Václav
V
Slaninová
Jiřina
J
D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D019075:Electrophoresis, Capillary; D006461:Hemolysis / Q000187:drug effects*; D008826:Microbial Sensitivity Tests
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C534036:melectin