Mitova Maya I, Murphy Annabel C, Lang Gerhard, Blunt John W, Cole Anthony L J, Ellis Gill, Munro Murray H G
Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
J Nat Prod. 2008 Sep;71(9):1600-3. doi: 10.1021/np800221b. Epub 2008 Aug 15.
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).
通过将高效液相色谱生物活性分析/微量滴定技术与毛细管核磁共振仪器相结合，并利用抗海洋生物数据库，传统的评估/分离去重复/表征程序可以大幅缩短。以从新西兰寄生真菌金孢隔指孢的分离物中分离出一种新的肽菌素——金黄肽菌素（1）为例，说明了这种方法。通过使用高效液相色谱生物活性分析/微量滴定板分析结合毛细管核磁共振仪器和抗海洋生物数据库，通过生物活性导向分级分离识别出了金黄肽菌素的独特性质。二维核磁共振技术与质谱裂解实验相结合，确定了金黄肽菌素（1）的平面结构，而氨基酸残基的绝对构型则通过马尔菲方法确定。金黄肽菌素（1）对P388小鼠白血病细胞系具有细胞毒性（IC50为6.61微摩尔），并对枯草芽孢杆菌表现出显著活性（IC50为1.54微摩尔）。
