Synthesis of analogs of K-582A, an antibiotic heptapeptide.
K-582 A, an antibiotic heptapeptide, has a sequence of H-L-Arg-L-Arg(OH)-D-Orn-L-Thr-D-Orn-L-Lys-D-Tyr-OH (Arg(OH), threo-gamma-hydroxyarginine). In order to investigate the relationship between structure and antimicrobial activity, four shortened analogs, des-L-Arg1, L-Arg(OH)2-K582 A (pentapeptide), des-L-Arg(OH)2-K-582 A (hexapeptide) and their N-acetyl derivatives, were synthesized by the conventional method. None of them, however, showed any antimicrobial activity. Three more analogs, [L-Lys2]K-582 A, [L-Orn2]K-582 A and [L-Arg2]K-582 A, were synthesized. Among them, only [L-Arg2]K-582 A showed substantial activity against Candida krusei and Saccharomyces rouxii, indicating that the presence of a guanidyl side chain at position 2 is an essential factor for the induction of activity.
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D023181:Antimicrobial Cationic Peptides; D001412:Bacillus subtilis / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis*; D011487:Protein Conformation; D012440:Saccharomyces / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D007202:Indicators and Reagents; D010455:Peptides; C026530:myroridin K