FLUORESCENCE LIFE ON BIS INTERCALATING DAUNOMYCIN ANALOGS IN VIABLE CELLS

一些新的双嵌插型蒽环类抗生素， 我们设计并合成了柔红霉素的类似物 合作者的实验室。这些新化合物的合理设计 是基于单体蒽环类药物与DNA结合的几何构型 在高分辨率晶体结构中观察到的寡核苷酸。 柔红霉素的单体单位通过它们的 阳离子糖胺部分上的反应性3‘NH2取代基来形成这些 双苯并环类药物。由于不同的细胞内结合复合体 可以通过荧光寿命来区分和定量 分析，我们将使用这种方法来检测这些新的绑定 毒剂到不同的亚细胞成分。从这样的决定 负责细胞毒性的药物络合物可能被确定。 基于已知的新型潜在抗癌药物的设计 结构原理和绑定属性可用于生成 具有显著增加的D-NA结合亲和力的化合物和 有趣的生物活动。

A number of new bis-intercalating anthracycline antibiotics, analogs of daunomycin, have been designed and synthesized in our collaborator's laboratory. The rational design of these new compounds was based upon the geometry of monomeric anthracyclines bound to DNA oligonucleotides observed in high-resolution crystal structures. Monomeric units of daunorubicin have been linked through their reactive 3' NH2 substituents on the daunosamine moieties to form these bisanthracyclines. Since differential intracellular binding complexes can be distinguished and quantitated by fluorescence lifetime analyses, we will use this approach to detect binding of these new agents to different subcellular components. From such determinations those drug complexes responsible for cytotoxicity may be ascertained. The design of new potential anticancer agents based on known structural principles and binding properties can be used to produce a compound with significantly increased D NA binding affinity and with interesting biological activity.