A TRANSFERASE IN DISORAZOLE SYNTHASE

二甲拉唑合成酶中的转移酶

• 批准号: 8169903
• 负责人: IRIMPAN I MATHEWS
• 金额: $ 0.3万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169903
• 关键词: Antineoplastic Agents; Apoptosis; Binding; Catalysis; Cell Death; Cell Line; Cell division; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Epothilones; Funding; Grant; Institution; Lung; Microtubules; Multi-Drug Resistance; Ovarian; Paclitaxel; Pharmaceutical Preparations; Research; Research Personnel; Resources; Source; Transferase; Tubulin; United States National Institutes of Health; Vincristine; malignant breast neoplasm; polymerization

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 自从识别并使用紫杉醇治疗肺癌、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标。紫杉醇结合并稳定微管，导致细胞分裂停滞并最终导致细胞死亡。最近发现的与紫杉醇具有类似作用的化合物是埃博霉素和discodermolides，这两种化合物都处于临床试验阶段。 地索唑 A1 是来自 Sorangium cellulosum 菌株的 29 种相关大环聚酮化合物之一，已被证明可以抑制微管蛋白的聚合，在皮摩尔浓度下诱导细胞凋亡。 与长春新碱类药物相反，地索拉唑对多重耐药细胞系有效。 结构研究旨在了解地索唑合酶中转移酶的催化机制。