Explorative Solid-Phase Extraction (E-SPE) for Accelerated Microbial Natural Product Discovery, Dereplication, and Purification
Explorative Solid-Phase Extraction (E-SPE) for Accelerated Microbial Natural Product Discovery, Dereplication, and Purification
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DOI：
10.1021/np100151y
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发表时间：
2010-06-01
影响因子：
5.1
通讯作者：
Nielsen, Kristian F.
中科院分区：
文献类型：
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作者：
Mansson, Maria;Phipps, Richard K.;Nielsen, Kristian F.
微生物天然产物（NP）涵盖了高度的化学多样性，因此微生物提取物的分析和纯化往往很复杂。Antibase 2008中34390条记录的计算pK（a）值的分布分析显示，在pH 2-11范围内，所有纳入的化合物中有44%具有酸性官能团，17%具有碱性官能团，9%具有酸性官能团和碱性官能团。这表明了使用离子交换色谱作为分离过程的一个组成部分，正交的经典反相策略的巨大潜力。因此，我们研究了使用“探索性固相萃取”（E-SPE）协议，使用SAX，Oasis MAX，SCX和LH-20柱，有针对性地开发化学功能。E-SPE为化学和生物学分析提供了最少的级分（15），并暗示了制备规模方法的发展。总的来说，这允许快速提取物优先化、更容易的去复制、生物活性的映射和纯化策略的制定。
Microbial natural products (NP) cover a high chemical diversity, and in consequence extracts from microorganisms are often complex to analyze and purify. A distribution analysis of calculated pK(a) values from the 34390 records in Antibase2008 revealed that within pH 2-11, 44% of all included compounds had an acidic functionality, 17% a basic functionality, and 9% both. This showed a great potential for using ion-exchange chromatography as an integral part of the separation procedure, orthogonal to the classic reversed-phase strategy. Thus, we investigated the use of an "explorative solid-phase extraction" (E-SPE) protocol using SAX, Oasis MAX, SCX, and LH-20 columns for targeted exploitation of chemical functionalities. E-SPE provides a minimum of fractions (15) for chemical and biological analyses and implicates development into a preparative scale methodology. Overall, this allows fast extract prioritization, easier dereplication, mapping of biological activities, and formulation of a purification strategy.