Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
Chem Commun (Camb). 2019 Aug 1;55(63):9379-9382. doi: 10.1039/c9cc03051d.
Small-molecule natural products have been an essential source of pharmaceuticals to treat human diseases, but very little is known about their behavior inside dynamic, live human cells. Here, we demonstrate the first structure-activity-distribution relationship (SADR) study of complex natural products, the anti-cancer antimycin-type depsipeptides, using the emerging bioorthogonal Stimulated Raman Scattering (SRS) Microscopy. Our results show that the intracellular enrichment and distribution of these compounds are driven by their potency and specific protein targets, as well as the lipophilic nature of compounds.
小分子天然产物一直是治疗人类疾病的药物的重要来源，但对于它们在动态的、活的人类细胞内的行为知之甚少。在这里，我们使用新兴的生物正交受激拉曼散射（SRS）显微镜，首次对具有抗癌作用的安密霉素型两性脂肽等复杂天然产物进行了结构-活性-分布关系（SADR）研究。我们的研究结果表明，这些化合物在细胞内的富集和分布是由其效力和特定的蛋白质靶标以及化合物的亲脂性所驱动的。
