Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides
Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides
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DOI：
10.3762/bjoc.16.8
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发表时间：
2020-01-09
影响因子：
2.7
通讯作者：
Sewald, Norbert
中科院分区：
文献类型：
--
作者：
Mueller, Sabrina;Paulus, Jannik;Sewald, Norbert
偶氮苯是能够在肽或小分子中的E-to-Z光异构化后产生显著结构变化的光可切换分子，从而控制几何形状和功能性。E-to-Z光异构化通常在350 nm（π-π * 跃迁）照射时实现，而Z-to-E异构化在>400 nm（n-pi* 跃迁）或热照射时进行光化学反应。光可切换化合物经常被用作模块，例如，来控制蛋白质和DNA的相互作用。然而，它们与小沟结合咪唑/吡咯（Im/Py）聚酰胺结合使用是前所未有的。Dervan型Im/Py聚酰胺配备有偶氮苯单元，即，3-（3-（氨甲基）苯基）偶氮苯乙酸，作为两条Im/Py聚酰胺链之间的连接体。只有（Z）-偶氮苯的聚酰胺结合到小沟的双链DNA发夹。光异构化通过1H-1 NMR实验示例性地评估，而（Z）-偶氮苯衍生物的小沟结合通过CD滴定实验证明。结合配体的诱导圆二色性（ICD）带，连同双链DNA解链温度的光度测定，揭示了与配体缔合后DNA的显着稳定。（Z）-偶氮苯作为结构单元诱导反转，这有利于吡咯/咪唑酰胺与DNA碱基之间的氢键。相比之下，E-构型的聚酰胺不诱导任何ICD特征的小沟结合。光可切换偶氮苯单元的掺入是获得能够仅在Z-构型中与dsDNA小沟相互作用的光可切换Im/Py发夹聚酰胺的有希望的策略。
Azobenzenes are photoswitchable molecules capable of generating significant structural changes upon E-to-Z photoisomerization in peptides or small molecules, thereby controlling geometry and functionality. E-to-Z photoisomerization usually is achieved upon irradiation at 350 nm (pi-pi* transition), while the Z-to-E isomerization proceeds photochemically upon irradiation at >400 nm (n-pi* transition) or thermally. Photoswitchable compounds have frequently been employed as modules, e.g., to control protein-DNA interactions. However, their use in conjunction with minor groove-binding imidazole/pyrrole (Im/Py) polyamides is yet unprecedented. Dervan-type Im/Py polyamides were equipped with an azobenzene unit, i.e., 3-(3-(aminomethyl)phenyl)azophenylacetic acid, as the linker between two Im/Py polyamide strands. Only the (Z)-azobenzene-containing polyamides bound to the minor groove of double-stranded DNA hairpins. Photoisomerization was exemplarily evaluated by H-1 NMR experiments, while minor groove binding of the (Z)-azobenzene derivatives was proven by CD titration experiments. The resulting induced circular dichroism (ICD) bands of the bound ligands, together with the photometric determination of the dsDNA melting temperature, revealed a significant stabilization of the DNA upon association with the ligand. The (Z)-azobenzene acted as a building block inducing a reverse turn, which favored hydrogen bonds between the pyrrole/imidazole amide and the DNA bases. In contrast, the E-configured polyamides did not induce any ICD characteristic for minor groove binding. The incorporation of the photoswitchable azobenzene unit is a promising strategy to obtain photoswitchable Im/Py hairpin polyamides capable of interacting with the dsDNA minor groove only in the Z-configuration.