Energy minimized structures of carcinogen-DNA adducts: 2-acetylaminofluorene and 2-aminofluorene.
Energy minimized structures of carcinogen-DNA adducts: 2-acetylaminofluorene and 2-aminofluorene.
复制标题
致癌物-DNA 加合物的能量最小化结构：2-乙酰氨基芴和 2-氨基芴。
DOI：
10.1080/07391102.1986.10506355
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发表时间：
1986
影响因子：
4.4
通讯作者：
Broyde,S
中科院分区：
文献类型：
--
作者：
Hingerty,BE;Broyde,S
本文报道了芳香胺2-乙酰氨基芴（AAF）和2-氨基芴（AF）修饰的DNA的能量最小化结构。这些已经计算出一个新的分子力学程序，专门设计来定义这种加合物所施加的扭曲，并采用合理的策略，搜索与共价连接的致癌物的DNA分子的构象空间。在交替的G-C序列中，AAF加合物优选位于未变形的Z-螺旋的外部。它也可以诱导碱基置换，伴随变性和螺旋弯曲的序列不利于Z型，但不包括未变形的B螺旋。相比之下，AF加合物更喜欢未受干扰的B-螺旋的大沟，但也可以在DNA的单链区域（如复制叉）诱导致癌物碱基堆积。这两种加合物不同的生物学性质可能与它们不同的构象特征有关。
Energy minimized structures of DNA modified by the aromatic amines 2-acetylaminofluorene (AAF) and 2-aminofuorene (AF), for which no experimental atomic resolution data exist, are presented. These have been computed with a new molecular mechanics program specifically designed to define distortions imposed by such adducts, and employing a rational strategy for searching the conformation space of a DNA molecule with covalently linked carcinogen. In alternating G-C sequences, the AAF adduct prefers to reside at the exterior of an undeformed Z-helix. It can also induce base displacement with attendant denaturation and helix bending in sequences that disfavor the Z form, but undeformed B helices are excluded. The AF adduct, by contrast, prefers the major groove of an unperturbed B-helix, but can also induce carcinogen-base stacking in single stranded regions of the DNA, such as at the replication fork. The different biological properties of these two adducts may be related to their distinct conformational features.