GLYCOSYLTRANSFERASES AS DRUG TARGETS IN MYCOBACTERIA

描述：(改编自申请者摘要)分枝杆菌细胞壁 在分枝杆菌发病机制中，合成是一个潜在的干预点。 研究人员将设计和合成分枝杆菌抑制剂。 Rhap和GALF酶(在哺乳动物细胞中都没有发现)。具体来说， 分枝杆菌鼠李糖基供体和受体类似物- 利用核苷二磷酸糖供体的半乳糖基转移酶 UDP-半乳呋喃糖和TDP-鼠李糖。此外，调查人员将使 在糖的受体位置结合和抑制的二糖 转移酶。这些化合物将用肉汤稀释液进行体外筛选。 测定和无细胞测定转移酶。选定的活性化合物将是 在巨噬细胞实验和小鼠结核病模型中进行体外和体内筛选， 分别进行了分析。

DESCRIPTION: (Adapted from Applicant's Abstract) Mycobacterial cell wall synthesis is a potential point of intervention in mycobacterial pathogenesis. The investigators will design and synthesize inhibitors of mycobacterial enzymes rhap and galf (neither are found in mammalian cells). Specifically, glycosyl donor and acceptor analogs of mycobacterial rhamnosyl- galactosyltransferases that utilize nucleoside diphosphate sugar donors UDP-galactofuranose and TDP-rhamnopyranose. Also, the investigators will make disaccharides that bind and inhibit in the acceptor site of the sugar transferases. These compounds will be screened in vitro using a broth dilution assay and cell-free assay transferase. Selected active compounds will be screened in vitro and in vivo in a macrophage assay and a murine TB model, respectively.