New Nucleotide Pairs for Stable DNA Triplexes Stabilized by Stacking Interaction

Abstract

New nucleotide pairs applicable to formation of DNA triplexes were developed. We designed oligonucleotides incorporating 5-aryl deoxycytidine derivatives (dC5Ars) and cyclic deoxycytidine derivatives, dCPPP and dCPPI, having an expanded aromatic area, as the second strand. As pairing partners, two types of abasic residues (C3: propylene linker, phi: abasic base) were chosen. It was concluded that, when the 5-aryl-modified cytosine bases paired with the abasic sites in TFOs in a space-fitting manner, the stability of the resulting triplexes significantly increased. The recognition of C3 toward dC5Ars was selective because of the stacking interactions between their aromatic part and the nucleobases flanking the abasic site. These results indicate the potential utility of new nucleotide triplets for DNA triplex formation, which might expand the variety of structures and sequences and might be useful for biorelated fields such as DNA nanotechnologies.

Nucleotides and Nucleic Acids; Oligo- and Polynucleotides

“…178,179 The expanded cytosine analogue (41) has been used for triplex stabilisation, as the extended aromatic ring system projects into the major groove and aids stability of a third strand by additional stacking interactions. 180 2 0 -O-Methyl-2-thiouridine was found to be more stable than the corresponding uracil when incorporated into either DNA or RNA oligonucleotides, though both the uracil and 2-thiouracil derivatives showed the same base discrimination. 181,182 2-Thioribothymidine (s 2 T) is a modified RNA analogue found in tRNA where it aids stabilisation of the tRNA structure.…”

Computational evaluation of the stability of 2′-O-methyl-RNA/RNA duplexes incorporating 3-deazaguanine derivatives by ab initio calculations and a molecular dynamics simulation

“…The stacking interaction energy was dependent on the overlapping area [33,34]. As shown in Table 3, the intrastrand and interstrand overlapping area energies in the subsystems decreased in the order of S3 (11.6 Å 2 ) > S2 (11.1 Å 2 ) > S1 (10.4 Å 2 ) and S2 (8.3 Å 2 ) > S3 (8.0 Å 2 ) > S1 (5.7 Å 2 ), respectively, whereas the corresponding intrastrand and interstrand stacking energies in the subsystems decreased in the order of S3 (À27.7 kcal/mol) > S1 (À25.8 kcal/ mol) > S2 (À24.7 kcal/mol) and S3 (À6.6 kcal/mol) > S1 (À6.1 kcal/mol) > S2 (À5.5 kcal/mol), respectively.…”

Controlling the Fluorescence of Benzofuran‐Modified Uracil Residues in Oligonucleotides by Triple‐Helix Formation

“…studies. [38][39] As the 5-arylpyrimidine residue, we selected fluorescent 5-(benzofuran-2-yl)uracil (Ura BF ) because of its high fluorescence quantum yield (F) and fluorescence increase dependence on DNA-DNA hybridization. [35] We further designed its derivative 5-(3-methylbenzofuran-2-yl)uracil (Ura MBF ).…”

“…As shown in Figure 1 A, the benzofuran moieties of Ura BF and Ura MBF when located in the major groove can rotate when the oligodeoxynucleotide containing them forms a duplex with target nucleic acids. However, upon binding to triplex-forming oligonucleotides (TFOs) with a propylene linker (C3) [38][39] at the counter position of the Ura BF or Ura MBF , the benzofuran ring becomes sandwiched between two bases. These flanking bases make the benzofuran and uracil rings coplanar (Figure 1 B), thus inducing fluorescence.…”

“…However, upon binding to triplex-forming oligonucleotides (TFOs) with a propylene linker (C3) [38][39] at the counter position of the Ura BF or Ura MBF , the benzofuran ring becomes sandwiched between two bases. These flanking bases make the benzofuran and uracil rings coplanar (Figure 1 B), thus inducing fluorescence.…”