距离比较法(DISCO)构建原卟啉原氧化酶抑制剂药效团模型

在原卟啉原氧化酶(Protox)三维结构未知情况下,利用距离比较法(DISCO),将8个具有代表性结构特征的Protox抑制剂,与其作用底物(基质)原卟啉原IX(ProtogenIX)的分子构象进行迭合,建立了可能的药效团模型;并据此确定了ProtogenIX与Protox相互作用时,可能采取的活性构象。这些信息将有助于设计、开发新型Protox抑制剂。

Study on pharmacophore model of protox inhibitors by DISCO method

Protoporphyrinogen oxidase (Protox) is the molecular target of a large number of herbicides. These herbicides compete with protoporphyrinogen IX (Protogen IX) , the substrate of Protox, at or near the catalytic site on Protox. In this paper, taking Protogen IX as reference compound, eight of typical Protox inhibitors were superimposed to fit with their most favorite conformation to build Protox' s pharmacophore model by using distance - comparisons (DISCO) method without the three - dimensional structures of Protox. Based on these, a probable active conformation of Protogen was conformed when the interaction occurred between the Protogen IX and Protox. All of these are useful clues for designing novel Protox inhibitors.