A TRANSFERASE IN DISORAZOLE SYNTHASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 自从紫杉醇被发现并用于治疗肺癌、卵巢癌和乳腺癌以来，微管一直是抗癌药物的一个有吸引力的靶点。紫杉醇结合并稳定微管，导致细胞分裂停滞，最终细胞死亡。最近发现的与紫杉醇类似作用的化合物是埃博西酮和盘状糖苷，这两种化合物都在临床试验中。从一株纤维索兰菌中分离得到的29个相关大环多酮之一的二奥拉唑A1，已被证明能抑制微管蛋白的聚合，在皮摩尔浓度下诱导细胞凋亡。与长春新碱组药物不同，地索拉唑对多药耐药细胞系有效。结构研究旨在了解异丙唑合酶中转移酶的催化作用机理。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Microtubules have been an attractive target for anticancer drugs since the identification and use of taxols for the treatment of lung, ovarian, and breast cancers. Taxol binds to and stabilizes microtubules, resulting in an arrest in cell division and eventual cell death. Compounds identified more recently with a similar action to taxol are the epothilones and discodermolides, both of which are in clinical trials. The disorazole A1, one of 29 related macrocyclic polyketides from a strain of Sorangium cellulosum, has been shown to inhibit the polymerization of tubulin, inducing apoptosis at picomolar concentrations. In contrast to the vincristine group of drugs, disorazoles are effective against multidrug-resistant cell lines. The structural study is aimed at understanding the mechanism of the catalysis of a transferase in disorazole synthase.