Conformation of the deoxydinucleoside monophosphate dCpdG modified at carbon 8 of guanine with 2-(acetylamino)fluorene.
Conformation of the deoxydinucleoside monophosphate dCpdG modified at carbon 8 of guanine with 2-(acetylamino)fluorene.
复制标题
用 2-(乙酰氨基)芴修饰鸟嘌呤碳 8 的脱氧二核苷单磷酸 dCpdG 的构象。
DOI：
10.1021/bi00256a034
复制
发表时间：
1982
期刊：
影响因子：
2.9
通讯作者：
Broyde,S
中科院分区：
文献类型：
--
作者：
Hingerty,B;Broyde,S
B. Hingerty and S. Broyde* abstract: Minimized conformational potential energy cal-culations were performed for dCpdG modified with the car-cinogen 2-(acetylamino) fluorene (AAF). The major adduct, linked via a covalent bond between guanine C-8 and N-2 of AAF, was investigated. The 12 variable torsion angles and both deoxyribose puckers were independent flexible parameters in the energy minimizations. Three categories of low-energy conformers were calculated in which the guanine was syn and nearly perpendicular to the plane of the fluorene:(1) forms in which fluorene is stacked with cytidine (included among these is theglobal minimum energy conformation);(2) con-formers which preserve guanine-cytidine stacking while placing the fluorene in a base-pair obstructing position;(3) conformers which maintain guanine-cytidine stacking and place the fluorene at the helix exterior, without interfering with base pairing. The Z form is important in this group. In addition, a low-energy conformation with guanine anti, but still nearly perpendicular to fluorene, was computed. Molecular models were constructed for the most important conformations incorporated into larger polymers. These indicated that the fluorene-cytidine stacked forms induce a severe kink in the B helix. Conformers with guanine-cytidine stacking and AAF in a base-pair obstructing position place the AAF at the B-type helix interior with little distortion in the helix direction. Conformers with the guanine-cytidine stack in which AAF does not affect base pairing place the fluorene at the Z or alternate helix exterior. It is suggested that base sequence, extent of modification, and external conditions such as salt concentration determine which of a number of possible con-formational effects is actually induced by AAF. The variety of observed experimental results withAAF-modified DNA may reflect these various conformational possibilities. e carcinogen TV-acetoxy-2-(acetylamino) fluorene (AAAF) links covalently to DNA. In vitro, the major adduct (about f From the Biology Division, Oak Ridge National Laboratory, Oak
