CORE--CHEMICAL SYNTHESIS SUPPORT FACILITY

该核心将提供以下领域的合成化学：1。海藻糖和脊髓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）。负责真菌酸合成的关键酶的竞争性抑制剂，如一些去饱和酶（项目1）。过渡态类似物设计用于抑制鼠李糖吡喃糖基、阿拉伯糖呋喃糖基和半乳糖呋喃糖基转移酶，促进检测开发（项目4）。合成放射性标记的阿拉伯糖烷酰核苷酸，以确定它们是否是十烯丙基- p -Araf （C50-P-Araf）中Araf单元的直接和唯一前体，其本身是聚合Araf的来源，促进了分析开发（项目4）。合成[1-14C]- β - D-arabinofuranosyl-1-mono-phosporyl decaprenyl （C50-P-[14C] Araf）用于研究阿拉伯糖基转移酶作为药物开发靶点（项目4）。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和这些步骤的抑制（项目4）。

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).