Müller Sabrina, Paulus Jannik, Mattay Jochen, Ihmels Heiko, Dodero Veronica I, Sewald Norbert
Organic and Bioorganic Chemistry, Department of Chemistry, Bielefeld University, PO Box 100131, D-33501 Bielefeld, Germany.
Organic Chemistry I, Department of Chemistry, Bielefeld University, PO Box 100131, D-33501 Bielefeld, Germany.
Beilstein J Org Chem. 2020 Jan 9;16:60-70. doi: 10.3762/bjoc.16.8. eCollection 2020.
Azobenzenes are photoswitchable molecules capable of generating significant structural changes upon to- photoisomerization in peptides or small molecules, thereby controlling geometry and functionality. to- photoisomerization usually is achieved upon irradiation at 350 nm (π-π* transition), while the to- isomerization proceeds photochemically upon irradiation at >400 nm (n-π* 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 ()-azobenzene-containing polyamides bound to the minor groove of double-stranded DNA hairpins. Photoisomerization was exemplarily evaluated by H NMR experiments, while minor groove binding of the ()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 ()-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 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 configuration.
偶氮苯是可光开关分子，在肽或小分子中进行光异构化时能够产生显著的结构变化，从而控制几何形状和功能。光异构化通常在350nm（π-π跃迁）照射下实现，而光异构化在>400nm（n-π跃迁）照射下通过光化学方式进行或通过热方式进行。可光开关化合物经常被用作模块，例如用于控制蛋白质-DNA相互作用。然而，它们与小沟结合咪唑/吡咯（Im/Py）聚酰胺结合使用尚未有先例。Dervan型Im/Py聚酰胺配备了偶氮苯单元，即3-(3-(氨基甲基)苯基)偶氮苯乙酸，作为两条Im/Py聚酰胺链之间的连接体。只有含()-偶氮苯的聚酰胺与双链DNA发夹的小沟结合。通过1H NMR实验示例性地评估了光异构化，而通过CD滴定实验证明了()偶氮苯衍生物的小沟结合。结合配体产生的诱导圆二色性（ICD）带，连同双链DNA解链温度的光度测定，揭示了与配体结合后DNA的显著稳定。()-偶氮苯作为诱导反向转折的结构单元，有利于吡咯/咪唑酰胺与DNA碱基之间形成氢键。相比之下，构型的聚酰胺没有诱导任何小沟结合的ICD特征。引入可光开关的偶氮苯单元是一种有前景的策略，可获得仅在构型下能够与双链DNA小沟相互作用的可光开关Im/Py发夹聚酰胺。
