结核药物先导物埃库米星的发现与表征
Discovery and characterization of the tuberculosis drug lead ecumicin.
作者信息
Gao Wei, Kim Jin-Yong, Chen Shao-Nong, Cho Sang-Hyun, Choi Jongkeun, Jaki Birgit U, Jin Ying-Yu, Lankin David C, Lee Ji-Ean, Lee Sun-Young, McAlpine James B, Napolitano José G, Franzblau Scott G, Suh Joo-Won, Pauli Guido F
机构信息
†Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
‡Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, United States.
出版信息
Org Lett. 2014 Dec 5;16(23):6044-7. doi: 10.1021/ol5026603. Epub 2014 Nov 19.
Abstract
The new tuberculosis (TB) lead ecumicin (1), a cyclic tridecapeptide, was isolated from Nonomuraea sp. MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS(2). Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey's analysis.
摘要
新型抗结核先导化合物ecumicin（1）是一种环状十三肽，在针对抗结核活性的高通量筛选中，从野野村菌属MJM5123中分离得到。通过液相色谱-高分辨质谱检测到其分子量为1599原子质量单位，这使得最初难以推断其分子式。通过广泛的核磁共振实验确定了各个结构单元。通过液相色谱-质谱联用（2）区分了由此得到的两种可能的平面结构。通过X射线晶体学和马尔菲法分析确定了绝对构型并明确了结构。
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