SYNTHESIS OF ANTIINFECTIVE AGENTS

抗感染剂的合成

• 批准号: 6169388
• 负责人: SAMUEL J DANISHEFSKY
• 金额: $ 39.17万
• 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/6169388
• 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：(主要研究人员)该计划的总体目标 是：(1)发展战略的进展和发现 在有机合成中实现有价值的反应和(Ii) 这些发现有助于促进人类健康。当我们继续我们的长期合作 对合成天然抗感染药物感兴趣，我们 还包括细胞毒性抗肿瘤药物，特别是当一种新的 对其作用机制进行了推测。此外，在这个节目中，我们 继续我们的探索，开发和评估新的疫苗结构以促进 对肿瘤发生和转移的免疫力。 在我们将尝试综合的具体目标结构中有 (I)可归类为 马钱子苷(包括马钱子素、沙丁菌素和valdivone A) (刺五加酶具有紫杉醇样作用。 微管蛋白解聚)，(Ii)螺旋霉素和相关结构 如红霉素和紫红霉素(螺旋霉素是首次报道 DNA解旋酶抑制剂)，(Iii)沙拉霉素B，一种有效的抗生素 对革兰氏阳性菌的作用，(Iv)有效的优丹明B 抗疟疾激素和(V)前列环素，它是一种有效的PKC抑制剂和 IL-8受体的抑制物。此外，(Vi)我们继续就 新的第二代和第三代的设计、综合和评估 作为抗癌疫苗评估的构建物。这项调查的范围 包括取代(或增加)KLH的脂类结合物，簇生 在粘蛋白中呈现模拟抗原的呈现，以及抗原 类似物，希望能引发更具侵略性的免疫反应。