Evolving trends in the dereplication of natural product extracts. 2. The isolation of chrysaibol, an antibiotic peptaibol from a New Zealand sample of the mycoparasitic fungus Sepedonium chrysospermum.
By the application of an HPLC bioactivity profiling/microtiter technique in conjunction with capillary NMR instrumentation and access to the AntiMarin database the conventional evaluation/isolation dereplication/characterization procedures can be dramatically truncated. This approach is illustrated using the isolation of a new peptaibol, chrysaibol (1), from a New Zealand isolate of the mycoparasitic fungus Sepedonium chrysospermum. The unique nature of chrysaibol was recognized by bioactivity-guided fractionation using HPLC bioactivity profiling/microtiter plate analysis in conjunction with capillary NMR instrumentation and the AntiMarin database. 2D NMR techniques, in combination with MS fragmentation experiments, determined the planar structure of chrysaibol (1), while the absolute configurations of the amino acid residues were defined by Marfey's method. Chrysaibol (1) was cytotoxic against the P388 murine leukemia cell line (IC50 6.61 microM) and showed notable activity against Bacillus subtilis (IC50 1.54 microM).
Mitova
Maya I
MI
Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
Murphy
Annabel C
AC
Lang
Gerhard
G
Blunt
John W
JW
Cole
Anthony L J
AL
Ellis
Gill
G
Munro
Murray H G
MH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006999:Hypocreales / Q000737:chemistry*; D007941:Leukemia P388; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009520:New Zealand; D054848:Peptaibols
D000900:Anti-Bacterial Agents; D001688:Biological Products; D054848:Peptaibols; C532705:chrysaibol