CORE--CHEMICAL SYNTHESIS SUPPORT FACILITY

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复合物的分枝菌酰转移酶活性，这将为结核病药物提供模型，并提供与分枝菌酸沉积最终途径相关的信息（项目1;具体目标3）。2.负责合成分枝菌酸的关键酶的竞争性抑制剂，如一些去饱和酶（项目1）。3.过渡态类似物设计用于抑制吡喃鼠李糖基、阿拉伯呋喃糖基和呋喃半乳糖基转移酶，促进检测开发（项目4）。4.合成放射性标记的阿拉伯呋喃糖基核苷酸，以确定它们是否是十异戊二烯基-β-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，促进测定开发（项目4）。5.合成[1- 14 C]-β-D-阿拉伯呋喃糖基-1-单磷酰基癸烯基（C50-P-[14 C] Araf），以研究作为药物开发靶点的阿拉伯糖基转移酶（项目4）。6.合成简单的糖基受体，研究细胞壁生物合成的各个方面，特别是阿拉伯聚糖和半乳聚糖片段的生物合成以及这些步骤的抑制（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).