Synthesis of Antiinfective Agents

抗感染剂的合成

• 批准号: 6775516
• 负责人: SAMUEL J DANISHEFSKY
• 金额: $ 49.34万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-03-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6775516
• 关键词: Synthesis; Antiinfective; Agents

DESCRIPTION (provided by applicant): The long term goals of our laboratory involve the achievement of advances in the capabilities in chemical synthesis and the applications of these advances to problems of biological and even medicinal import. At the chemistry level, we select novel and challenging small molecule natural products structures, which will serve to stimulate and exemplify the value of new strategies and new reaction methodologies. In this facet of our "small molecule" work, we place particular emphasis on conciseness of approach, convergence, and stereocontrol. In parallel we have a program addressed to the chemical synthesis of complex oligosaccharides, in the context of polypeptide or protein like conjugates. In this effort, we place particular emphasis on novel glycosylation protocols and, seek out particular retrosynthetic disconnections and protection strategies which enable conciseness of the synthetic effort. In this program we seek to enlarge upon our capacity to build complex oligosaccharides into the context of substantial polypeptide or even protein settings. For this AI-16943-25-29 grant period, we have identified eight (8) programs for exploration: (1) migrastatin - as its name implies, this compound is reported to prevent tumor cell migration. As such, it might provide the basis for a significant drug candidate in angiogenesis; (2) brasilicardin - an immunosuppressive agent; (3) garsubellin - this compound is exemplary of a fascinating series of non-peptidal small molecules which exhibit neuronal growth factor activity; (4)tashironin - this compound is substantially dissimilar to garsubellin. It also exhibits non-peptidal NGF activity; (5) NG0187 - this compound is a polyoxygenated steroid-like system which also exhibits non-peptidal nerve growth factor activity; (6) Asparagine linked glycopolypeptide constructs which simulate the key structural features of PSA (prostate specific antigen); (7) the synthesis of constructs which simulate the key features of GP120. Aside from the chemical challenge, implicit in this goal is the hope to induce an antibody response which could be of value in progression of the evolution of AIDS disease; (8) A long term goal of the complex glycoconjugate program is the total synthesis of a functional erythropoietin (EPO).

描述（由申请人提供）：我们实验室的长期目标涉及实现化学合成能力的进步以及将这些进步应用于生物甚至医药进口问题。在化学层面，我们选择新颖且具有挑战性的小分子天然产物结构，这将有助于激发和体现新策略和新反应方法的价值。在我们“小分子”工作的这一方面，我们特别强调方法的简洁性、收敛性和立体控制。与此同时，我们还有一个针对多肽或类蛋白质缀合物的复杂寡糖化学合成的计划。在这项工作中，我们特别强调新的糖基化方案，并寻找特定的逆合成断开和保护策略，以实现合成工作的简洁性。在这个项目中，我们寻求扩大我们在大量多肽甚至蛋白质环境中构建复杂寡糖的能力。在 AI-16943-25-29 资助期内，我们确定了八 (8) 个探索项目：(1) migrastatin - 顾名思义，据报道该化合物可防止肿瘤细胞迁移。因此，它可能为血管生成方面的重要候选药物提供基础； (2)巴西卡定——免疫抑制剂； (3) 加苏贝林 - 该化合物是一系列令人着迷的非肽小分子的典范，具有神经元生长因子活性； (4)他代罗宁——该化合物与加苏贝林有很大不同。它还表现出非肽 NGF 活性； (5) NG0187——该化合物是一种多氧类固醇样系统，也表现出非肽神经生长因子活性； (6)天冬酰胺连接的糖多肽构建体，其模拟PSA（前列腺特异性抗原）的关键结构特征； (7)模拟GP120关键特征的构建体的合成。除了化学挑战之外，这一目标还隐含着希望诱导抗体反应，这可能对艾滋病疾病的进化进程有价值； (8) 复合糖复合物计划的长期目标是功能性促红细胞生成素 (EPO) 的全合成。