CORE--CHEMICAL SYNTHESIS SUPPORT FACILITY

核心——化学合成支撑设施

• 批准号: 6340744
• 负责人: Patrick Joseph Brennan
• 金额: $ 11.4万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340744
• 关键词: antitubercular agents; biomedical facility; chemical synthesis; drug discovery /isolation

This Core will provide synthetic chemistry in the following areas: 1. Trehalose and cord factor analogs designed to inhibit the mycolyltransferase activity of the antigen 85 complex which will provide models for tuberculosis drugs and also information relevant to the final pathways for mycolic acid deposition (Project 1; Specific Aim 3). 2. Competitive inhibitors of key enzymes responsible for the synthesis of mycolic acid such as some of the desaturases (Project 1). 3. Transition state analogs designed to inhibit rhamnopyranosyl, arabinofuranosyl, and galactofuranosyl transferases, facilitating assay development (Project 4). 4. Synthesis of radiolabeled arabinofuranosyl nucleotides in order to see whether they are the direct and only precursors of the Araf unit in decaprenyl-P-Araf (C50-P-Araf), itself the source of polymerized Araf, facilitating assay development (Project 4). 5. Synthesis of [1-14C]-beta- D-arabinofuranosyl-1-mono-phosporyl decaprenyl (C50-P-[14C] Araf) to study arabinosyltransferases as targets for drug development (Project 4). 6. Synthesis of simple glycosyl group acceptors, to study aspects of cell wall biosynthesis, specifically biogenesis of the arabinan and galactan segments and inhibition of these steps (Project 4).

该核心将在以下领域提供合成化学：1.海藻糖和脐带因子类似物，旨在抑制抗原85复合体的霉菌转移酶活性，这将为结核病药物提供模型，并提供与霉菌酸沉积的最终途径相关的信息(项目1；具体目标3)。2.负责合成霉菌酸的关键酶的竞争性抑制物，例如一些去饱和酶(项目1)。3.旨在抑制鼠李糖基、阿拉伯呋喃糖基和半乳糖基呋喃糖基转移酶的过渡态类似物，促进分析方法的发展(项目4)。4.合成放射性标记的阿拉伯呋喃葡萄糖核苷酸，以确定它们是否是十碳烯基-P-Araf(C50-P-Araf)中Araf单位的直接和唯一前体，而C50-P-Araf本身就是聚合Araf的来源，促进了分析的发展(项目4)。5.合成[1-14C]-β-D-阿拉伯呋喃糖基-1-单磷酰基十氢戊二烯(C50-P-[14C]Araf)，以研究阿拉伯糖基转移酶作为药物开发的靶标(项目4)。6.简单糖基受体的合成，研究细胞壁生物合成的各个方面，特别是阿拉伯糖和半乳聚糖片段的生物发生以及这些步骤的抑制(项目4)。