A fluorescent metallointercalator conjugate that selectively targets DNA base mismatches has been synthesized by coupling an organic fluorophore to a bulky Rh intercalator containing the chrysenequinone diimine ligand. Ion pairing between the cationic Rh and anionic fluorophore moieties dramatically quenches the fluorescence of the conjugate in solution and in the presence of matched DNA. However, in the presence of mismatched DNA, the fluorescence of the conjugate is increased >300%. This increase in fluorescence is attributed to the loss in intramolecular quenching associated with DNA binding; intercalation of the Rh moiety into the mismatched site can lead to electrostatic repulsion of the anionic fluorophore away from the DNA phosphate backbone and Rh. Denaturing PAGE experiments with ^(32)P-labeled oligonucleotides indicate that the conjugate selectively binds the mismatched DNA with a binding affinity of 6 × 10^5 M^(-1) and, upon irradiation, cleaves the DNA backbone neighboring the mismatched site.
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机译：通过将有机荧光团偶联到含有瓜醌二亚胺配体的大体积Rh嵌入剂上，已经合成了选择性靶向DNA碱基错配的荧光金属嵌入剂共轭物。阳离子Rh和阴离子荧光团部分之间的离子配对可显着淬灭溶液中和存在匹配DNA时缀合物的荧光。然而，在DNA错配的情况下，缀合物的荧光增加> 300％。荧光的这种增加归因于与DNA结合相关的分子内猝灭的损失。 Rh部分插入错配位点会导致阴离子荧光团从DNA磷酸骨架和Rh上静电排斥。用^（32）P标记的寡核苷酸进行变性PAGE实验表明，缀合物以6×10 ^ 5 M ^（-1）的结合亲和力选择性结合错配的DNA，并在照射后切割错配位点附近的DNA骨架。 。
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