Structural and biological evaluation of some loloatin C analogues.
Loloatin C is a cyclic cationic antimicrobial peptide which is active against gram positive as well as certain gram negative bacteria. Unfortunately, it is equally potent against human erythrocytes. To probe the structure-activity relationship of this promising antibiotic peptide, amino acid substitution and/or incorporation of a constraint sugar amino acid dipeptide isoster has been applied. Six new derivatives have been synthesized using SPPS and their solution structure investigated using NMR studies. Finally, the antimicrobial and the hemolytic activities have been determined.
Tuin
Adriaan W
AW
Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Grotenbreg
Gijsbert M
GM
Spalburg
Emile
E
de Neeling
Albert J
AJ
Mars-Groenendijk
Roos H
RH
van der Marel
Gijsbert A
GA
Noort
Daan
D
Overkleeft
Herman S
HS
Overhand
Mark
M
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010456:Peptides, Cyclic; C545032:loloatin C