Ornstein R L, Rein R
Chem Biol Interact. 1979 Oct;27(2-3):291-311. doi: 10.1016/0009-2797(79)90133-9.
Intercalation of the carcinogen 4-nitroquinoline 1-oxide (4-NQO) or its metabolic intermediate forms, probably precedes the covalent bond formation of the ultimate carcinogenic form with DNA. A 'complete' empirical-potential energy description of the base-sequence and metabolite specificities of the 4-NQO intercalation process is presented in this work. The important force and structural interaction components are depicted via decomposed energy functions. Energy-minimized intercalated complexes are presented and indicate several interesting characteristics. It is clear that the various intercalated quinoline-metabolites do not generally enter into 'strictly' parallel-planar stacked orientations (unlike the structurally rigid ethidium-intercalated complexes). Intercalation is energetically permitted for six of seven quinoline-metabolites (QMS) studied, although, intercalation into to Pyr(3'-5')Pur sequences is preferred over Pur(3'-5'1Pyr sequences. The three quinoline-metabolites that are more energetically favoured to undergo intercalation than the parent form are also known to enter into the greatest amount of covalent interactions with DNA and its constituents. Thus the present work further suggests the existence of a two-step binding mechanism: intercalation followed by covalent reaction.
致癌物4-硝基喹啉1-氧化物（4-NQO）或其代谢中间形式的嵌入，可能先于最终致癌形式与DNA形成共价键。本研究给出了4-NQO嵌入过程的碱基序列和代谢物特异性的“完整”经验势能描述。通过分解能量函数描绘了重要的力和结构相互作用成分。给出了能量最小化的嵌入复合物，并显示出几个有趣的特征。显然，各种嵌入的喹啉代谢物通常不会进入“严格”的平行平面堆叠取向（与结构刚性的溴化乙锭嵌入复合物不同）。在所研究的七种喹啉代谢物（QMS）中，有六种在能量上允许嵌入，尽管嵌入Pyr(3'-5')Pur序列比Pur(3'-5'1Pyr序列更受青睐。与母体形式相比，在能量上更有利于发生嵌入的三种喹啉代谢物，也已知会与DNA及其成分发生最多的共价相互作用。因此，本研究进一步表明存在两步结合机制：嵌入后进行共价反应。
