Fragment screening against the thiamine pyrophosphate riboswitch thiM
Fragment screening against the thiamine pyrophosphate riboswitch thiM
复制标题
DOI：
10.1039/c0sc00406e
复制
发表时间：
2011-01-01
期刊：
影响因子：
8.4
通讯作者：
Smith, Alison G.
中科院分区：
文献类型：
--
作者：
Cressina, Elena;Chen, Liuhong;Smith, Alison G.
核糖开关是mRNA的区域，其选择性地结合某些代谢物，从而调节基因表达。我们已经开发出一种方法，它使用生物物理技术（平衡透析，waterLOGSY和T-2弛豫编辑的NMR光谱和等温滴定量热法）的组合，允许筛选和识别核糖开关的新配体。通过这种方法，在E.大肠杆菌硫胺素焦磷酸（TPP）核糖开关thiM，导致17个命中的鉴定。这些化合物的K-D值为22 ~ 670 μ M，其中有4种化合物的KD值
Riboswitches are regions of mRNA that bind selectively certain metabolites, thereby regulating gene expression. We have developed a method, which uses a combination of biophysical techniques (equilibrium dialysis, waterLOGSY and T-2 relaxation-edited NMR spectroscopy and isothermal titration calorimetry) that allows screening and identification of novel ligands for riboswitches. By this method a library of 1300 fragments was screened on the E. coli thiamine pyrophosphate (TPP) riboswitch thiM, resulting in the identification of 17 hits. The compounds showed K-D values from 22 to 670 mu M, with four compounds having KD values