BIS INTERCALATING DAUNOMYCIN ANALOGS IN VIABLE CELLS: MEASURE FLUORESCENCE LIFE

BIS 在活细胞中插入道诺霉素类似物：测量荧光寿命

• 批准号: 6298017
• 负责人: WALDEMAR PRIEBE
• 金额: $ 0.36万
• 依托单位: UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6298017
• 关键词: biological products; biomedical resource; 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 DNA binding affinity and with interesting biological activity.

一些新的双插层蒽环类抗生素， 柔红霉素的类似物，已经在我们的实验室中设计和合成， 合作者的实验室。 这些新化合物的合理设计 是基于与DNA结合的单体蒽环类抗生素的几何结构 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已经通过它们的 在道诺糖胺部分上的反应性3'NH 2取代基，以形成这些 双蒽环类 由于差异细胞内结合复合物 可以通过荧光寿命来区分和定量 我们将使用这种方法来检测这些新的 不同的亚细胞成分。 从这样的决心 可以确定那些引起细胞毒性的药物复合物。 基于已知的潜在抗癌药物的设计 结构原理和结合性质可用于产生 具有显著增加的DNA结合亲和力和 有趣的生物活动。