CHEMICAL AND BIOLOGICAL STUDIES IN CANCER CHEMOTHERAPY

癌症化疗的化学和生物学研究

• 批准号: 3163241
• 负责人: THOMAS J BARDOS
• 金额: $ 11.78万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-11-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163241
• 关键词: DNA; DNA directed DNA polymerase; DNA directed RNA polymerase; antimetabolites; aziridines; chemical synthesis; cytotoxicity; drug adverse effect; drug design /synthesis /production; drug metabolism; hypoxia; neoplasm /cancer radiation therapy; nucleoside analog; oligonucleotides; radiation sensitivity; radiopharmacology; radioprotective agents; thymidylate synthase; transfer RNA

The objectives of the proposed research are: 1. To determine the structure-activity relationships and mode of action of the 2,2-dimethyl phosphoraziridines as radiation potentiating antitumor agents and to optimize the design of new agents. This involves the synthesis of new compounds designed to have either phosphorylating or alkylating activities, or both; comparative studies of their chemical and biochemical activities, and radiation potentiating effects in cell-culture systems and in animal tumors; and studies of the interaction of selected agents with DNA-repair at the molecular level and of their reactions with nucleic acid components. 2. To synthesize and study new derivatives of partially thiolated polynucleotides designed to improve their selectivity and/or stability as antitemplates (inhibitors) of DNA polymerases in vitro and in vivo, and to synthesize and study modified oligonucleotides of known base sequences as specific "antiprimers" of reverse transcriptases. Studies include physicochemical characterization, stability to nucleases, inhibition of polymerases, and cytotoxicity.

拟议研究的目标是：1。确定 2,2-二甲基的结构活性关系和作用方式 磷酸核苷作为辐射增强抗肿瘤剂并优化 新代理商的设计。 这涉及设计新化合物设计的 具有磷酸化或烷基化活性，或两者兼而有之；比较 研究其化学和生化活性以及辐射增强的研究 细胞培养系统和动物肿瘤的影响；和研究 选定药物与分子水平和DNA修复的相互作用 它们与核酸成分的反应。 2。综合和研究新的 旨在改善其的部分硫醇化多核苷酸的衍生物 选择性和/或稳定性作为DNA聚合酶的抗孕激素（抑制剂） 体外和体内，并合成并研究的修饰的寡核苷酸 已知的碱序列是逆转录酶的特定“抗抗二聚体”。 研究包括物理化学表征，对核酸酶的稳定性， 聚合酶和细胞毒性的抑制作用。