High-resolution MS, MS/MS, and UV database of fungal secondary metabolites as a dereplication protocol for bioactive natural products.
High-resolution MS, MS/MS, and UV database of fungal secondary metabolites as a dereplication protocol for bioactive natural products.
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DOI：
10.1021/np4004307
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发表时间：
2013-09-27
影响因子：
5.1
通讯作者：
Oberlies NH
中科院分区：
文献类型：
--
作者：
El-Elimat T;Figueroa M;Ehrmann BM;Cech NB;Pearce CJ;Oberlies NH
从天然产物中发现新的生物活性化合物的主要问题是已知化合物的重新分离。这样的重新分离浪费了时间和资源，分散了化学家对更有希望的线索的注意力。为了解决这个问题，需要去复制策略，使得能够在开始分离努力之前筛选粗提取物中已知化合物的存在。在从丝状真菌中鉴定抗癌药物先导物的项目中，出现了显著的去复制挑战，因为源材料的分类学很少已知，因此，不能探测文献以鉴定可能的已知化合物。建立了超高效液相色谱-光电二极管阵列-高分辨串联质谱（UPLC-PDA-HRMS-MS/MS）分析真菌次生代谢产物的方法。通过记录真菌代谢产物的HRMS和MS/MS光谱，利用正离子化和负离子化模式构建数据库。还记录了其他详细信息，如紫外吸收最大值和保留时间。显示细胞毒性活性的小规模培养物在进行放大或纯化过程之前被去复制。使用这些方法，在对已知化合物进行可靠鉴定后，可以从进一步研究中消除约50%的细胞毒性浸提液。这种去复制方法的具体属性包括专注于真菌的生物活性次级代谢产物，使用10分钟色谱法，并包括HRMS和MS/MS数据。
A major problem in the discovery of new biologically active compounds from natural products is the re-isolation of known compounds. Such re-isolations waste time and resources, distracting chemists from more promising leads. To address this problem, dereplication strategies are needed that enable crude extracts to be screened for the presence of known compounds before isolation efforts are initiated. In a project to identify anticancer drug leads from filamentous fungi, a significant dereplication challenge arises, as the taxonomy of the source materials are rarely known, and, thus, the literature cannot be probed to identify likely known compounds. An ultra-performance liquid chromatography-photodiode array-high-resolution tandem mass spectrometric (UPLC-PDA-HRMS-MS/MS) method was developed for dereplication of fungal secondary metabolites in crude culture extracts. A database was constructed by recording HRMS and MS/MS spectra of fungal metabolites, utilizing both positive- and negative-ionization modes. Additional details, such as UV-absorption maxima and retention times, were also recorded. Small-scale cultures that showed cytotoxic activities were dereplicated before engaging in the scale-up or purification processes. Using these methods, approximately 50% of the cytotoxic extracts could be eliminated from further study after the confident identification of known compounds. The specific attributes of this dereplication methodology include a focus on bioactive secondary metabolites from fungi, the use of a 10-min chromatographic method, and the inclusion of both HRMS and MS/MS data.
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影响因子：
3.3
作者：
ARGOUDELIS, AD
通讯作者：
ARGOUDELIS, AD
影响因子：
3.3
作者：
Bertinetti, Brenda V.;Alejandra Rodriguez, M.;Cabrera, Gabriela M.
通讯作者：
Cabrera, Gabriela M.
影响因子：
2.1
作者：
Ayers, Sloan;Ehrmann, Brandie M.;Adcock, Audrey F.;Kroll, David J.;de Blanco, Esperanza J. Carcache;Shen, Qi;Swanson, Steven M.;Falkinham, Joseph O., III;Wani, Mansukh C.;Mitchell, Sheila M.;Pearce, Cedric J.;Oberlies, Nicholas H.
通讯作者：
Oberlies, Nicholas H.
影响因子：
3
作者：
Blackwell, Meredith
通讯作者：
Blackwell, Meredith
影响因子：
5.1
作者：
Dong, JY;He, HP;Zhang, KQ
通讯作者：
Zhang, KQ