SYNTHESIS OF BLEOMYCIN GROUP ANTIBIOTICS AND ANALOGUES

描述：（主要研究者）本研究的长期目标 研究内容为：1）博莱霉素类抗生素的合成及开发 （二）促进其拟订的新方法， 作为治疗剂具有优良上级性质的博来霉素类似物， 其可用于帮助确定博来霉素的作用机制。 在所要求的支助期间，具体目标包括完成 腐草霉素的全合成和立体控制的腐草霉素的全合成 他利霉素 还计划合成博来霉素类似物， 可以帮助定义DNA结合的模式，其结合并切割RNA， 更大的亲和力，并且在双链中表现出更高的效率 B型DNA的裂解。 虽然博来霉素是临床上常用的药物， 尽管使用了抗肿瘤剂，但是在抗肿瘤药物中存在许多缺陷。 了解BLM作为抗肿瘤剂发挥作用的方式。 的 这里提出的研究应有助于理解的机制， BLM行动，并有可能确定BLM同系物表现出 增强了作为抗肿瘤剂的性能。

DESCRIPTION: (Principal Investigator's) The long term goals of this research are i) synthesis of bleomycin group antibiotics and the development of new methods that facilitate their elaboration, and ii) synthesis of bleomycin analogues that have superior properties as therapeutic agents or which can be used to help define the mechanism of action of bleomycin. For the period of requested support, the specific aims include completion of the total synthesis of phleomycin and a stereocontrolled, total synthesis of tallysomycin. Also planned are the syntheses of bleomycin analogues that can help to define the mode of DNA binding, which bind and cleave RNA with greater affinity, and which exhibit greater efficiency in double-strand cleavage of B-form DNA. While bleomycin is an established member of the armamentarium of clinically used antitumor agents, there are nonetheless a number of deficiencies in the understanding of the way in which BLM functions as an antitumor agent. The studies proposed here should facilitate an understanding of the mechanism of BLM action and make it possible to identify BLM congeners exhibiting enhanced properties as antitumor agents.