生物合理方法设计合成新型除草剂

Bio-rational Design Synthesis of Novel Herbicides

采用生物合理的方法设计合成了光合作用抑制剂及ALS酶抑制剂,根据绿色红假单胞菌(Rps.viridis)光合反应中心X-衍射的晶体结构同源模建了高等植物豌豆(Pisum sativum)D1蛋白的结构模型,及其与抑制剂氰基丙烯酸(酰胺)与氢化脲嘧啶的复合物模型.研究了D1蛋白与抑制剂可能的作用位点.为了提高筛选的力度,还应用Wang树脂引入了组合合成的方法.对三类AIS抑制剂进行了2D-QSAR,3-DQSAR,作用模型及新抑制剂的设计研究.

The method of bio-rational design was applied for designing two novel herbicides, photosystem 11 inhibitor and ALS inhibitor. Based on the photosystem reaction center's X-ray crystal structure of Rps. viridis, the 3D-structure of Pisum sativum 32 Kdal protein (D1) was constructed with homology modeling method. The molecular modeling of cyanoacrylates (cyanoacrylamides) with D1 protein of Pisum sativum have been presented. Studies show that the binding force includes mainly H-bond interaction, Van der Waals and pi-ring stacking interaction. It was found that SER 268 in D1 protein might be an important binding site. Thus some new cyanoacrylates (cyanoacrylamides) were designed and synthesized. For rapid optimization, combinatorial methods were introduced to synthesize 3-N-substituted (2-thio) hydrouracils library using Wang resin. For the AIS inhibitors, their 2D-QSAR, 3D-QSAR analysis, action model and molecular design of nlovel inhibitors were discussed.