DNA major versus minor groove occupancy of monomeric and dimeric crystal violet derivatives. Toward structural correlations
DNA major versus minor groove occupancy of monomeric and dimeric crystal violet derivatives. Toward structural correlations
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DOI：
10.1016/j.bmc.2023.117438
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发表时间：
2023-09-25
影响因子：
3.5
通讯作者：
Minehan，Thomas
中科院分区：
文献类型：
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作者：
Mirzakhanian，Aren;Khoury，Michael;Minehan，Thomas
合成了三苯甲烷染料结晶紫(CV)的六个单体(1a-1f)和五个二聚体(2a-2e)衍生物。通过竞争荧光插层置换(FID)分析、粘度实验以及UV和CD光谱对这些化合物与CT DNA结合的评价表明，单体衍生物1a和二聚体衍生物2d可能与DNA的主槽结合，而二聚体衍生物2a和2e可能与DNA的小槽结合。从ITC实验和主要的沟槽结合限制酶BamHI对DNA切割的不同抑制中获得了这些衍生物沟槽占有率分配的额外证据，如琼脂糖凝胶电泳所显示的那样。数据表明，主要沟槽配体可能是由含有立体大体积的3，5-二甲基-N，N-二甲基苯胺基的染料单元构成的；此外，烯烃系留二聚体2D的沟槽选择性表明，配体与DNA之间的立体电子相互作用(n=→和π*)也是制备主要沟槽结合配体的重要设计考虑因素。
Six monomeric (1a-1f) and five dimeric (2a-2e) derivatives of the triphenylmethane dye crystal violet (CV) have been prepared. Evaluation of the binding of these compounds to CT DNA by competitive fluorescent intercalator displacement (FID) assays, viscosity experiments, and UV and CD spectroscopy suggest that monomeric derivative 1a and dimeric derivative 2d likely associate with the major groove of DNA, while dimeric derivatives 2a and 2e likely associate with the minor groove of DNA. Additional evidence for the groove occupancy assignments of these derivatives was obtained from ITC experiments and from differential inhibition of DNA cleavage by the major groove binding restriction enzymeBamHI, as revealed by agarose gel electrophoresis. The data indicate that major groove ligands may be optimally constructed from dye units containing a sterically bulky 3,5-dimethyl-N,N-dimethylaniline group; furthermore, the groove-selectivity of olefin-tethered dimer 2d suggests that stereoelectronic interactions (n → π*) between the ligand and DNA are also an important design consideration in the crafting of major-groove binding ligands.