Application of a Metal‐Mediated Base Pair to the Detection of Medicinally Relevant Single Nucleotide Polymorphisms

Abstract

A highly stabilizing metal‐mediated base pair formed from the canonical nucleobase cytosine (C), the transition metal ion AgI, and the artificial nucleobase 1H‐imidazo[4,5‐f][1,10]phenanthroline (P) was used in the generation of molecular beacons for the detection of medicinally relevant single nucleotide polymorphisms (SNPs) based on either a C→T or a T→C transition (T: thymine). The beacons exploit the fact that a P–C pair is strongly stabilized in the presence of AgI, whereas a P–T pair is significantly destabilized. A direct correlation of oligonucleotide sequence, duplex stability prior to the addition of AgI, stabilization due to metal‐mediated base pair formation, and performance of the molecular beacon was not observed. Nonetheless, the data show for the first time that metal‐mediated base pairing can be applied in the detection of medicinally relevant SNPs.

Concomitant Site‐Specific Incorporation of Silver(I) and Mercury(II) Ions into a DNA Duplex

“…In the first set of experiments, duplex III was incubated with a stoichiometric amount of Ag I at pH 5.5, resulting in an increase in T m of 4 °C (Figure a, Table S3). This value is in the same order of magnitude as previously found in other sequence contexts, albeit being at the lower end ,. Considering the non‐existence of P ‐Ag I ‐ T ‐H base pairs under these conditions, the formation of a P ‐Ag I ‐ C base pair (Scheme b) can be concluded.…”

Stable Hg(II)-mediated base pairs with a phenanthroline-derived nucleobase surrogate in antiparallel-stranded DNA

“…Similarly, other nucleic acid topologies and nucleic acid analogues have been probed with respect to the site-specific incorporation of metal ions in analogy to metal-mediated base-pair formation [28][29][30][31]. Several promising applications have already been established in this area, including the construction of structures with a modified electrical response [32,33], switchable devices [34], responsive devices [35,36], regulated primer extension [37], the specific detection of canonical nucleobases [38,39], the generation of DNA-templated metal nanoclusters [40], an expansion of genetic four-letter code [41], etc. Due to their accessibility from commercial resources, canonical nucleobases involved in metal-mediated base pairing have been most extensively studied, giving rise to C-Ag(I)-C and T-Hg(II)-T pairs [42].…”

Stable Copper(I)‐Mediated Base Pairing in DNA

“…[5] Even organometallic metal-mediated base pairs are known. [7] Metal-based functionalization of nucleic acids was applied, for example,inthe stabilization of parallel-stranded duplexes, [8] in modifying the charge transfer properties of DNA, [9] in the generation of DNA-templated noble metal nanoclusters, [10] and in the development of sensors for various analytes [11] and of metal-responsive materials. Theformation of arrays of metal ions within nucleic acids was confirmed by various crystal structures and solution NMR structures.…”

“…Theformation of arrays of metal ions within nucleic acids was confirmed by various crystal structures and solution NMR structures. [7] Metal-based functionalization of nucleic acids was applied, for example,inthe stabilization of parallel-stranded duplexes, [8] in modifying the charge transfer properties of DNA, [9] in the generation of DNA-templated noble metal nanoclusters, [10] and in the development of sensors for various analytes [11] and of metal-responsive materials. [12] We recently introduced 1H-imidazo[4,5-f][1,10]phenanthroline (P,S cheme 1) as an artificial nucleobase for metal-mediated base pairing [13] and successfully established an Ag I -mediated P-Ag I -P homo base pair.…”