AQSIQ Key Laboratory of Drug Detection, Fujian International Travel Healthcare Center, Fujian Entry-Exit Inspection and Quarantine Bureau of P.R.C., Fujian, 350001, China.
Environ Sci Pollut Res Int. 2013 Dec;20(12):8355-63. doi: 10.1007/s11356-013-1760-4. Epub 2013 May 5.
Perfluoroalkyl acids (PFAAs) are carcinogens, and elucidating their DNA binding properties is crucial for understanding PFAA genotoxicity. We have investigated the binding mode and affinity of five PFAAs to seven DNA molecules using fluorescence displacement and molecular docking analysis. DNA conformational changes upon PFAA binding were also examined by circular dichroism (CD). The data revealed that DNA intercalation was the dominant interaction mode of the PFAAs; however, these molecules also bound to grooves. The dissociation constants for the PFAAs ranged between 0.11 and 1,217.14 μM, and between 3.46 and 2,141.21 μM for DNA intercalation and groove binding, respectively. PFAAs that contain longer carbon chains had stronger DNA intercalation affinities. Binding to DNA was stronger for perfluoroalkyl sulfonates than for perfluorcarboxyl acids that contain the same number of carbons. This observation is postulated to arise from the presence of more fluorine and oxygen atoms in perfluoroalkyl sulfonates acting as hydrogen bond donors that facilitate stronger DNA intercalation. The binding of the PFAAs to DNA showed some CT-DNA sequence selectivity. Molecular docking analysis confirmed the DNA binding mode and affinities of the PFAAs. CD analysis revealed that the PFAAs weakened DNA base stacking and loosened DNA helicity. The present study has improved our understanding of the formation of PFAA-DNA adducts.
全氟烷基酸（PFAAs）是致癌物质，阐明其与 DNA 的结合特性对于理解 PFAAs 的遗传毒性至关重要。我们使用荧光置换和分子对接分析研究了五种 PFAAs 与七种 DNA 分子的结合模式和亲和力。还通过圆二色性（CD）研究了 PFAAs 结合后 DNA 构象的变化。数据表明，PFAAs 的主要相互作用模式是 DNA 嵌入；然而，这些分子也与沟槽结合。PFAAs 的离解常数在 0.11 到 1,217.14 μM 之间，对于 DNA 嵌入和沟槽结合分别在 3.46 到 2,141.21 μM 之间。含更长碳链的 PFAAs 与 DNA 的嵌入亲和力更强。含相同碳原子数的全氟烷基磺酸盐与全氟羧酸相比，与 DNA 的结合更强。据推测，这一观察结果源于全氟烷基磺酸盐中更多的氟和氧原子作为氢键供体，促进了更强的 DNA 嵌入。PFAAs 与 DNA 的结合显示出一定的 CT-DNA 序列选择性。分子对接分析证实了 PFAAs 的 DNA 结合模式和亲和力。CD 分析表明 PFAAs 削弱了 DNA 碱基堆积并使 DNA 螺旋松弛。本研究提高了我们对 PFAAs-DNA 加合物形成的理解。
