SYNTHETIC STUDIES RELATED TO CANCER RESEARCH & TREATMENT

与癌症研究相关的综合研究

• 批准号: 6120212
• 负责人: PAUL A WENDER
• 金额: $ 0.55万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6120212
• 关键词: biological products; biomedical resource; cardiovascular system; endocrine gland /system; enzymes; hematology; hormones; lipids; liver; lymphatic system; spectrometry; structural biology

This proposal describes a comprehensive program involving synthetic, mechanistic, biological, and computer modeling studies directed at the elucidation of the mode of action of demonstrated and of potential cancer chemotherapeutic agents, at the rational design and development of new classes of antitumor agents, and at the development of fundamentally new methodology and strategies for the synthesis of such agents. Five projects are proposed for investigation. A major continuation study will be directed at neocarzinostatin chromophore, the recently identified, structurally unprecedented, biologically active subunit of neocarzinostatin (NCS), a drug used in human cancer chemotherapy. Efforts will focus on determining the molecular basis for the antitumor activity of NCS, on establishing the basis for its DNA cleavage selectivity, on the utilization of this information in the rational design of new antitumor agents, and on the synthesis of simplified analogues and biological probes needed in support of these studies. A second major project is focussed on dynemicin A (Dyn A), an exciting new chemotherapeutic lead exhibiting significant in vitro and in vivo antitumor activity. Attention will be directed at the mechanism of activation of Dyn A, at the rational design and development of new Dyn A analogues, at the structural basis for its DNA lesion selectivity, and at an examination of a potentially biomimetic approach to its unprecedented structure. A third project is directed at the development of fundamentally new classes of DNA-cleaving agents and potential cancer chemotherapeutics that are designed to function by the transition metal, photochemical, and torsional induction of diradical formation. A fourth major effort is focussed on taxol, a compound whose recent, impressive clinical performance is likely to result in its imminent approval for use in cancer chemotherapy. This study is directed at the development of practical approaches to taxol analogues and at the elucidation of the structural requirements for taxol's activity. A final project entails completion of studies on the synthesis of aplysiatoxin. Overall, this research program is expected to be of significant value in chemistry, biology, and medicine.

该提案描述了一项综合计划，涉及 合成、机械、生物和计算机建模研究 旨在阐明已证明和的作用方式 潜在的癌症化疗药物的合理设计 和新型抗肿瘤药物的开发，以及 制定全新的方法和战略 此类试剂的合成。 拟定五个项目 调查。 一项主要的继续研究将针对 新制癌菌素发色团，最近发现的，结构 新制癌菌素（NCS）前所未有的生物活性亚基， 用于人类癌症化疗的药物。 努力的重点将是 确定 NCS 抗肿瘤活性的分子基础 为其 DNA 切割选择性奠定了基础 在新产品的合理设计中利用这些信息 抗肿瘤剂，以及简化类似物的合成 支持这些研究所需的生物探针。 第二专业 该项目的重点是动力霉素 A (Dyn A)，这是一种令人兴奋的新药物 化疗药物在体外和体内表现出显着的效果 抗肿瘤活性。 机制将受到关注 Dyn A的激活，在新Dyn的合理设计和开发中 类似物，在其 DNA 损伤选择性的结构基础上， 并检查其潜在的仿生方法 前所未有的结构。 第三个项目针对的是 开发全新类别的 DNA 切割剂以及 潜在的癌症化疗药物旨在通过 过渡金属、光化学和扭转感应 双自由基形成。 第四个主要努力集中在紫杉醇， 其最近令人印象深刻的临床表现可能是一种化合物 导致其即将被批准用于癌症化疗。 这 研究旨在开发紫杉醇的实用方法 类似物和结构要求的阐明 紫杉醇的活性。 最终项目需要完成以下研究 海兔毒素的合成。 总体而言，该研究计划是 预计在化学、生物学等领域具有重要价值 药品。