Lipkowitz K B, Chevalier T, Widdifield M, Beland F A
Chem Biol Interact. 1982 May;40(1):57-76. doi: 10.1016/0009-2797(82)90028-x.
The hepatocarcinogen N-hydroxy-2-acetylaminofluorene forms two C8-substituted deoxyguanosine adducts in vivo. The conformation of these adducts, as well as 2'-deoxyguanosine and 8-amino-2'-deoxyguanosine has been studied with Allinger's force field. Using the glycoside rotation as a reaction coordinate, multidimensional potential energy surface were determined by relaxing all internal degrees of freedom. The calculations indicate the 2'-deoxyguanosine should exist as a mixture of syn and anti forms, that the syn form is slightly favored for 8-amino-2'-deoxyguanosine, that N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-C8-AAF) will only be found in the syn conformation and that, although the syn form is also more stable for N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), it will have a substantially greater proportion of the anti-conformer than is found with dG-C8-AAF. The results of the force field calculations are discussed in relation to the effects these adducts may have on DNA structure.
肝癌致癌物N-羟基-2-乙酰氨基芴在体内形成两种C8取代的脱氧鸟苷加合物。利用Allinger力场研究了这些加合物以及2'-脱氧鸟苷和8-氨基-2'-脱氧鸟苷的构象。以糖苷旋转作为反应坐标，通过弛豫所有内部自由度确定多维势能面。计算表明，2'-脱氧鸟苷应以顺式和反式形式的混合物存在，8-氨基-2'-脱氧鸟苷的顺式形式略占优势，N-(脱氧鸟苷-8-基)-2-乙酰氨基芴(dG-C8-AAF)仅以顺式构象存在，并且尽管顺式形式对于N-(脱氧鸟苷-8-基)-2-氨基芴(dG-C8-AF)也更稳定，但它的反式构象比例将比dG-C8-AAF的大得多。结合这些加合物可能对DNA结构产生的影响，讨论了力场计算的结果。
