SYNTHESIS OF MYCOBACTERIAL ARABINOFURANOSYL METABOLITES

描述：(改编自申请者摘要)：This Fogarty 国际研究合作奖(FIRCA)旨在 了解结核分枝杆菌细胞壁的生物合成。这个 FIRCA支持具体目标1，以定义M。 结核将5-磷酸核糖焦磷酸(PRPP)转化为供体 十碳烯基磷酸-D-阿拉伯糖(DPA)。到目前为止，隔离 假定中间体5-磷酸碳基焦磷酸(PAPP)和 十碳烯基磷酸-5-磷酸-D-阿拉伯糖(5P-DPA)不成功， 可能是因为这些中间体立即转化为 合成途径中的后续化合物。合作者将 准备了可疑中间体PAPP和5P-DPA，然后PI将 确定它们是否可以转换为DPA。一旦这些或其他化合物 已经被证明是中间体，这项研究将扩展到使 DPA形成的潜在抑制剂。这些潜在的抑制物 将是PAPP和5P-DPA的类似物，并将使用 组合方法。这种方法将从多肽糖苷开始 阿拉伯糖-5-磷酸和HITS将在 药物化学方法。

DESCRIPTION: (Adapted from applicant's abstract): This Fogarty International Research Collaboration Award (FIRCA) is directed toward understanding cell wall biosynthesis in Mycobacterium tuberculosis. The FIRCA supports Specific Aim 1 to define the pathway by which M. tuberculosis converts 5-phosphoribosyl pyrophosphate (pRpp) into the donor decaprenylphosphate-D-arabinose (DPA). Thus far efforts to isolate the postulated intermediates 5-phosphoarbinosyl pyrophosphate (pApp) and decaprenylphosphate-5-phospho-D-arabinose (5P-DPA) have been unsuccessful, presumably because these intermediates are immediately transformed to subsequent compounds in the synthetic pathway. A collaborator will prepared the suspected intermediates pApp and 5P-DPA and the PI will then determine if they can be converted to DPA. Once these or other compounds have been shown to be intermediates, the research will be extended to make potential inhibitors of the formation of DPA. These potential inhibitors will be analogs of pApp and 5P-DPA and will be prepared using a combinatorial approach. This approach will start with peptide glycosides of arabinose-5-phosphate and hits will then be further refined in a medicinal chemical approach.