FLUORESCENCE LIFE ON BIS INTERCALATING DAUNOMYCIN ANALOGS IN VIABLE CELLS

双嵌段道诺霉素类似物在活细胞中的荧光寿命

• 批准号: 6327964
• 负责人: WALDEMAR PRIEBE
• 金额: $ 0.31万
• 依托单位: UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6327964
• 关键词: biomedical resource; human tissue; nucleic acids; proteins; technology /technique

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.

多种新型双嵌入蒽环类抗生素， 道诺霉素的类似物，已在我们的设计和合成 合作者的实验室。 这些新化合物的合理设计 基于与 DNA 结合的单体蒽环类药物的几何形状 在高分辨率晶体结构中观察到的寡核苷酸。 柔红霉素的单体单元通过其连接 道诺胺部分上的反应性 3' NH2 取代基形成这些 双蒽环类药物。 由于细胞内结合复合物存在差异 可以通过荧光寿命来区分和定量 分析中，我们将使用这种方法来检测这些新的结合 不同亚细胞成分的药物。 从这样的决定来看 可以确定那些负责细胞毒性的药物复合物。 基于已知的新的潜在抗癌药物的设计 结构原理和结合特性可用于产生 具有显着增加的 DNA 结合亲和力的化合物 有趣的生物活性。