Liu Xing-Hai, Chen Pei-Quan, Wang Bao-Lei, Li Yong-Hong, Wang Su-Hua, Li Zheng-Ming
The Research Institute of Elemento-Organic Chemistry, The State-Key Laboratory of Elemento-Organic Chemistry, National Pesticide Engineering Research Center, Nankai University, Tianjin 300071, China.
Bioorg Med Chem Lett. 2007 Jul 1;17(13):3784-8. doi: 10.1016/j.bmcl.2007.04.003. Epub 2007 Apr 6.
Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step in branched-chain amino acid biosynthesis. The catalyzed process consists of two stages, the first of which is an alkyl migration from one carbon atom to its neighbouring atom. The likely transition state is a cyclopropane derivative, thus a series of new cyclopropane derivatives, such as 1-cyano-N-substituted-cyclopropanecarboxamide, were designed and synthesized. Their structures were verified by (1)H NMR, FTIR spectrum, MS and elemental analysis. The K(i) values of active compounds 2, 4b against rice KARI were 95.30+/-13.71, 207.9+/-21.99 microM, respectively. The X-ray crystal structure of compound 4a was also determined. Auto-Dock was used to predict the binding mode of 4a. This was done by analyzing the interaction of the compounds 4a with the active sites of spinach KARI. This result was in accord with the result analyzed by the frontier molecular orbital theory.
酮醇酸还原异构酶（KARI；EC 1.1.1.86）催化支链氨基酸生物合成中的第二个共同步骤。催化过程包括两个阶段，第一阶段是烷基从一个碳原子迁移到其相邻原子。可能的过渡态是环丙烷衍生物，因此设计并合成了一系列新的环丙烷衍生物，如1-氰基-N-取代-环丙烷甲酰胺。通过¹H NMR、FTIR光谱、质谱和元素分析对其结构进行了验证。活性化合物2、4b对水稻KARI的抑制常数（Ki）值分别为95.30±13.71、207.9±21.99微摩尔。还测定了化合物4a的X射线晶体结构。使用自动对接来预测4a的结合模式。这是通过分析化合物4a与菠菜KARI活性位点的相互作用来完成的。该结果与前沿分子轨道理论分析的结果一致。
