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: 6280919
• 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: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6280919
• 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，