SYNTHESIS OF ANTIINFECTIVE AGENTS

抗感染剂的合成

• 批准号: 2886385
• 负责人: SAMUEL J DANISHEFSKY
• 金额: $ 38.03万
• 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 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2886385
• 关键词: antifungal agents; antiinfective agents; antimitotics; antineoplastic antibiotics; biological products; drug design /synthesis /production; immunosuppressive; neoplasm /cancer vaccine; stereochemistry

DESCRIPTION: (Principal Investigator's) The overall goals of this program are: (i) The development of advances in strategy and the discovery of enabling reactions of value in organic synthesis and (ii) the application of these findings to advance human health. While we continue our long term interest in the synthesis of naturally occurring antiinfectious agents, we also include cytotoxic antitumor agents, particularly where a novel mechanism of action has been inferred. Moreover, in this program we continue our quest to develop and evaluate new vaccine constructs to foster immunity against tumorgenesis and metastasis. Among the specific goal structures that we will attempt to synthesize are (i) class of marine derived natural products which can be classified as the eleuthesides (including eleutherobin, sarcodictyn and valdivone A) (eleutherobin has a demonstrated taxol like effect on the rate of microtubulin depolymerization), (ii) heliquinomycin and related structures such as rubromycin and purpuromycin (heliquinomycin is the first reported inhibitor of DNA helicase), (iii) saframycin B, an antibiotic with potent action against gram positive bacteria, (iv) yaoundamine B which is a potent antimalarial agen and (v) frondosin which is a potent PKC inhibitor and an inhibitor of IL-8 receptors. In addition, (vi) we continue our work on the design, synthesis and evaluation of new second and third generation constructs for evaluation as anticancer vaccines. The scope of this inquiry includes lipid conjugates to replace (or augment) KLH, clustered presentations to mimic antigen as presentations in mucins, and antigen analogs in the hope of triggering more aggressive immune responses.

描述：（主要研究者的）本计划的总体目标 是：（i）战略进步的发展和发现 实现有机合成中有价值的反应;（ii）应用 这些发现将促进人类健康。 当我们继续我们的长期 由于对天然抗感染剂的合成感兴趣，我们 还包括细胞毒性抗肿瘤剂，特别是当新型 的作用机制已经推断出来。 此外，在本计划中，我们 我们继续寻求开发和评估新的疫苗结构， 抗肿瘤发生和转移免疫。 我们将尝试综合的具体目标结构包括 (i)海洋衍生天然产品的类别，可归类为 五加苷（包括五加苷、肉珊瑚素和valdivone A） （五加苷素对细胞增殖率具有紫杉醇样作用， 微管蛋白解聚），（ii）螺旋霉素和相关结构 如红霉素和紫嘌呤霉素（heliquinomycin是首次报道的 DNA解旋酶抑制剂），（iii）Saframycin B，一种具有强效 对革兰氏阳性菌的作用，（iv）雅温得明B，其是一种有效的 抗疟阿根和（v）作为有效的PKC抑制剂的frondosin， IL-8受体抑制剂。 （六）继续开展工作， 新的第二代和第三代的设计、合成和评价 作为抗癌疫苗进行评价的构建体。 这次调查的范围 包括脂质缀合物以替代（或增加）KLH，成簇 在粘蛋白中呈现以模拟抗原，并且抗原 类似物，希望能引发更积极的免疫反应。