Rhodium-conjugate fluorescent probes for diagnostic of mismatched DNA

Abstract

In healthy cells, DNA base pair mismatches, as well as some other base pair anomalies derived from DNA base damage, are cor. through the mismatch repair (MMR) machinery. If left unrepaired, mismatches cause mutations, some of which promote cancerous transformations. Currently, there is a lack of effective mol. sensors for early cancer diagnosis. Therefore, developing mol. probes capable of detecting and signaling DNA base mismatches directly would be a powerful tool to this end. Previous studies have shown that rhodium metalloinsertors bind mismatches in double-strained DNA with high specificity. Nevertheless, these rhodium complexes show poor luminescence properties. Here we describe the design and study of rhodium conjugates tethered to environmentally sensitive fluorophore scaffolds. The fluorophore of choice is a cyanine dye where fluorescence emission strongly depends on its cis-/transphotoisomerization through excitation under appropriate wavelengths; photoisomerization, however, appears to be inhibited for DNA-binding by cyanine, leading to a signal-on emission. In our luminescent switches, the cyanine was covalently attached to a rhodium(III) metalloinsertor complex through a linear spacer i.e. polyamine or polyethylene glycol chain. The spectroscopic measurements in the presence of well matched and mismatched DNA support the notion that our systems are interesting probes for mismatch detection and signaling.

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