Fluorimetric and CD Recognition between Various ds-DNA/RNA Depends on a Cyanine Connectivity in Cyanine-guanidiniocarbonyl-pyrrole Conjugate

Abstract

Two novel isosteric conjugates of guanidiniocarbonyl-pyrrole and 6-bromo-TO (thiazole orange) were prepared, differing only in linker connectivity to cyanine (benzothiazole nitrogen vs. quinoline nitrogen). The quinoline analog was significantly more susceptible to aggregation in an aqueous medium, which resulted in induced circular dichroism (ICD; λ = 450–550 nm) recognition between A-T(U) and G-C basepair containing polynucleotides. The benzothiazole-isostere showed pronounced (four-fold) fluorimetric selectivity toward ds-RNA in comparison to any ds-DNA, at variance to its quinoline-analogue fluorescence being weakly selective to GC-DNA. Preliminary screening on human tumor and normal lung cell lines showed that both dyes very efficiently enter living cells and accumulate in mitochondria, causing moderate cytotoxic effects, and thus could be considered as lead compounds toward novel theragnostic mitochondrial dyes.

Selenium-Substituted Monomethine Cyanine Dyes as Selective G-Quadruplex Spectroscopic Probes with Theranostic Potential

“…Mostly, the compounds 1-6 did not show a stabilizing effect on ds-DNA and ds-RNA at ratio, r [compound]/[nucleotide phosphate] = 0.1 (Figures S27-S29 in SI). Only compound 5 with thiopropyl substituent on the N atom of the benzothiazolyl chromophore exhibited the stabilization effect on AT-DNA (∆T m value = 4 • C) [10,35,36]. Close derivative 6 with thioethyl substituent did not show any impact on DNA/RNA thermal stability.…”

“…For example, cyanine dyes with phosphonium substituents showed unusual kinetic recognition between minor grooves of homo and alternating AT-DNA sequences while guanidiniocarbonyl-pyrrole and bromo TO derivative enabled selective recognition of double-stranded (ds-) RNA vs. ds-DNA [8][9][10]. Similar discrimination between ds-DNA and ds-RNA structures was shown by oxazole yellow homodimer (YOYO), whereas chlorinated TOTO (thiazole orange homodimer) demonstrated preferential binding to alternating DNA sequences compared to non-halogenated TOTO [11].…”

Fluorescent Probes for Biomacromolecules Based on Monomethine Cyanine Dyes

“…The design of substituents in the terminal nuclei of MCDs can directly affect the interaction with biomacromolecules. In [49], two guanidiniocarbonyl-pyrrole conjugates (GCP) of MCDs were obtained (dyes 27 and 28; Figure 15), and their interaction with nucleotides was studied. The conjugates practically do not fluoresce in solution and exhibit strong fluorescence in the presence of dsRNA and dsDNA nucleotides.…”

“…New MCDs (dyes 100-103; Figure 26) were proposed as theranostic agents; the dyes showed cell growth-inhibitory effects on cancer cells (lines HCT 116; MCF-7 and H460) [21]. Screening against human lung carcinoma (A549) showed that guanidiniocarbonylpyrrole conjugates of MCDs accumulate effectively in cell mitochondria, causing moderate cytotoxic effects, which make them favorable for use in theranostics [49].…”