Covalently Mercurated Molecular Beacon for Discriminating the Canonical Nucleobases

Abstract

A highly nucleobase‐discriminating metalated nucleoside analogue, 3‐fluoro‐2‐mercuri‐6‐methylaniline, was incorporated into an oligonucleotide molecular beacon. Fluorescence emission spectra were measured after the addition of four different complementary strands, in which the nucleobase opposite the metalated analogue varies. The fluorescence results showed a clear binding selectivity at room temperature, in the order G>T>C>A. The selectivity is based on the different affinities between the metalated nucleoside analogue and the canonical nucleobases. The synthesized probe is capable of robust discrimination between the two purine as well as the two pyrimidine bases by fluorescence at room temperature, and more sophisticated temperature analysis allows clear separation of every canonical nucleobase. The probe would, hence, be a suitable method for the detection of single nucleotide polymorphisms.

Organomercury Nucleic Acids: Past, Present and Future

“…The identity of the base pairing partner was also clearly reflected in the 19 F chemical shift of 3‐fluoro‐2‐mercuri‐6‐methylaniline. The feasibility of SNP genotyping based on metal‐mediated base pairing was recently demonstrated with a molecular beacon ‐type probe incorporating the 3‐fluoro‐2‐mercuri‐6‐methylaniline in the middle of the recognition loop [103] . At appropriate temperature, stabilities of the different Hg II ‐mediated base pairs translated into different hairpin‐heteroduplex equilibria and further into different fluorescence emission intensities (Figure 4B).…”

“…The feasibility of SNP genotyping based on metal-mediated base pairing was recently demonstrated with a molecular beacon -type probe incorporating the 3-fluoro-2-mercuri-6-methylaniline in the middle of the recognition loop. [103] At appropriate temperature, stabilities of the different Hg II -mediated base pairs translated into different hairpin-heteroduplex equilibria and further into different fluorescence emission intensities (Figure 4B). Organomercury oligonucleotides, hence, hold great future potential as hybridization probes in SNP genotyping.…”

Towards polymerase-mediated synthesis of artificial RNA–DNA metal base pairs

“…1,2 Metal base pairs can be constructed using the canonical nucleobases or synthetic nucleoside analogs with nucleobases that are specifically designed to serve as ligands for the specific binding of transition metal cations. 3,4 These metal base pairs have advanced as promising candidates for a number of applications including the development of nanomolecular devices, 5 ion sensors and biosensing devices 6,7 and metal nanowires and nanodevices [8][9][10] as well as for the allosteric control of functional nucleic acids. [11][12][13][14] The formation of metal base pairs mainly occurs by annealing short synthetic oligonucleotides together with specific metal cations.…”

Triggering Copper(II)-Mediated Base Pair Formation by Light

“…In addition, the use of DNA with metal-mediated base pairs in asymmetric catalysis was proposed, too . Besides, metal-mediated base pairs are being discussed in the context of their application in the recognition of nucleic acid sequences and in the detection of single-nucleotide polymorphisms. − The ability to switch a particular nucleic acid property via the addition of metal ions is of great value in the development of stimuli-responsive DNA materials. In this context, metal-dependent DNAzymes and an aptamer were reported. − The capacity to trigger metal-mediated base pair formation by light represents a likewise important goal.…”