Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures.
Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures.
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DOI：
10.3390/molecules28155726
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发表时间：
2023-07-28
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影响因子：
--
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天然产物提供了无与伦比的小分子多样性，以推动药物筛选工作，但解卷积天然产物混合物的药理活性以识别关键的生物活性化合物仍然是一个令人烦恼和劳动密集型的过程。因此，我们已经开发了一个新的平台，通过鸟枪衍生与同位素标记的丙酸，活细胞亲和性测定，这是用来选择性地识别人口的化合物紧密结合的HeLa细胞培养物中，和计算LC-MS数据分析的同位素标记的化合物从细胞裂解物中存在于常见的膳食补充剂中的化合物的非特异性药理学潜力进行探测。数据分析表明，在每种提取物中成功衍生了数百种化合物，其中数十种化合物对HeLa细胞表现出高亲和力。总的来说，在三个独立的实验中筛选了超过一千种同位素标记的化合物的细胞亲和力，从而鉴定了几种具有特定蛋白质靶点的已知生物活性化合物和六种以前未报道的结构。新的天然产物包括从细花罗勒中分离得到的三个杜松醇类化合物和从缬草中分离得到的三个缬草生物碱。缬草生物碱是从缬草中分离出来的一个新的生物碱家族，可能具有以前未描述过的生物活性。这些结果共同证明了标记和阻碍工作流程作为药物发现方法的可行性。
Natural products provide an unparalleled diversity of small molecules to fuel drug screening efforts, but deconvoluting the pharmacological activity of natural product mixtures to identify key bioactive compounds remains a vexing and labor-intensive process. Therefore, we have developed a new platform to probe the non-specific pharmacological potential of compounds present in common dietary supplements via shotgun derivatization with isotopically labeled propanoic acid, a live cell affinity assay, which was used to selectively recognize the population of compounds which bind tightly to HeLa cells in culture, and a computational LC-MS data analysis of isotopically labeled compounds from cell lysate. The data analysis showed that hundreds of compounds were successfully derivatized in each extract, and dozens of those compounds showed high affinity for HeLa cells. In total, over a thousand isotopically labeled compounds were screened for cell affinity across three separate experiments, resulting in the identification of several known bioactive compounds with specific protein targets and six previously unreported structures. The new natural products include three tulsinol compounds which were isolated from Ocimum tenuiflorum and three valeraninium alkaloids from Valeriana officinalis. The valeraninium alkaloids constitute a distinct new family of alkaloids from valerian, which may have previously undescribed bioactivity. These results collectively demonstrate the tag and snag workflow’s viability as a drug discovery method.
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影响因子：
2.7
作者：
Martino, Emanuela;Della Volpe, Serena;Collina, Simona
通讯作者：
Collina, Simona
影响因子：
5.8
作者：
Murakami, Y;Shoji, M;Fujisawa, S
通讯作者：
Fujisawa, S
影响因子：
--
作者：
Becker A;Felgentreff F;Schröder H;Meier B;Brattström A
通讯作者：
Brattström A
DOI：
10.4103/0973-7847.95849
发表时间：
2012-01
期刊：
Pharmacognosy reviews
影响因子：
--
作者：
Petrovska BB
通讯作者：
Petrovska BB
影响因子：
120.1
作者：
Moffat, John G.;Vincent, Fabien;Prunotto, Marco
通讯作者：
Prunotto, Marco