Synthetic/Mechanistic Investigations of Antitumor Agents

抗肿瘤药物的合成/机理研究

• 批准号: 6633157
• 负责人: GARY ALLEN SULIKOWSKI
• 金额: $ 26.59万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6633157
• 关键词: FK506; antineoplastic antibiotics; dexamethasone; drug design /synthesis /production; enzyme inhibitors; glycosylation; oligosaccharides; protein tyrosine kinase

DESCRIPTION: (provided by applicant) This proposal describes the continuation of a research program involving the synthesis and mode of action studies of structurally complex natural products that have demonstrated unique antitumor activity. Three major projects are described. The first project involves synthetic and biological studies on apoptolidin a macrolide antitumor agent that induces transformed cells to undergo programmed cell death. We plan to continue development of a concise synthesis of apoptolidin and structural analogs designed to probe the cellular target of apoptolidin, an interaction presumed responsible for the unique onset of cell death. A second project is directed toward the synthesis of the structurally complex natural product hibarimicin B, a specific inhibitor of tyrosine kinase and oncogenic cell transformation. A third project is directed towards the development of a general method for the rapid assembly of 2-deoxy oligosaccharides, a frequent structural feature of natural antitumor antibiotics. Overall, this program is expected to have a significant impact on the areas of chemistry, biology and medicine.

描述：（由申请人提供）该提案描述了延续 涉及综合和作用模式研究的研究计划 结构复杂的天然产物，表现出独特的抗肿瘤作用 活动。描述了三个主要项目。第一个项目涉及 大环内酯类抗肿瘤药凋亡素的合成及生物学研究 诱导转化细胞经历程序性细胞死亡。我们计划 继续开发凋亡素的简明合成和结构 旨在探测细胞凋亡素（一种相互作用）的细胞靶标的类似物 推测负责细胞死亡的独特发生。第二个项目是 旨在合成结构复杂的天然产物 hibarimicin B，酪氨酸激酶和致癌细胞的特异性抑制剂 转变。第三个项目旨在开发 快速组装2-脱氧寡糖的通用方法，这是一种常见的方法 天然抗肿瘤抗生素的结构特征。总的来说，这个程序是 预计将对化学、生物学等领域产生重大影响 药品。