Double-headed nucleotides introducing thymine nucleobases in the major groove of nucleic acid duplexes

Abstract

Four different double-headed nucleosides each combining two thymine nucleobases with different linkers were synthesised. The 5-position of 2'-deoxyuridine was connected to the N1-position of a thymine through either m- or p-disubstituted phenyl or phenylacetylene linkers by the use of Suzuki or Sonogashira couplings. When introduced into oligonucleotides, the thermal stability of dsDNA and DNA : RNA duplexes were determined and structural information was obtained from CD- and fluorescence spectroscopy. Also the recognition of abasic sites was studied. In general, the more stable duplexes were obtained with m- rather than p-substitution and with phenylacetylene rather than phenyl linkers.

A double-headed nucleotide with two cytosines: DNA with condensed information and improved duplex stability

“…4,5 In this context, an interesting modification is the addition of a second nucleobase to the nucleotide skeletonthe so-called double-headed nucleotide. 6 We have previously reported the synthesis and recognition properties of several double-headed nucleotides with the additional nucleobase attached to the 5´-, 2´or 5-position through various linkers, [7][8][9][10][11][12][13][14][15][16][17] while others have used the 4´-position or the 2´-N of amino-LNA as attachment points. 18,19 For the dU B design (Fig.…”

Condensing the information in DNA with double-headed nucleotides

“…Beside its biological functionality, DNA has emerged as a convenient scaffold for two-and three-dimensional objects in nanotechnology 1,2 and information storage. 3,4 Recently, we [5][6][7][8][9][10][11][12][13][14][15] and others [16][17][18][19][20] have examined the potential of introducing a second nucleobase onto the existing nucleotide scaffold as a means of increasing the molecular diversity of DNA. These so-called bis-headed or double-headed nucleotides enable various intra or extra-helical contacts depending on the location of the second nucleobase.…”

Double‐Headed Nucleotides with Non‐Native Nucleobases: Synthesis and Duplex Studies

“…Column chromatography was performed with Silica Gel 60 (particle size 0.040-0.063 μm, Merck). 1 H NMR, 13 C NMR, 19 F NMR and 31…”

“…1 3 J CF = 19.9 Hz, C4''), 150.1 (C2), 141.9 (d, 5 J CF = 2.0 Hz, C8''), 140.5 (C6), 116.6 (d, 4 J CF = 3.7 Hz, C5''), 100.8 (C5), 84.6 (C1'), 79.5 (C4'), 78.9 (C2'), 75.5 (C3'), 60.4 (C5'), 45.7 (C6'), 17. 3 Hz, C6''), 151.0 (d, 3 J CF = 19.3 Hz, C4''), 150.5 (C2), 142.1 (d, 5 J CF = 1.9 Hz, C8''), 141.9 (C6), 116.6 (d, 4 J CF = 3.9 Hz, C5''), 100.5 (C5), 85.3 (C1'), 85.1 (C4'), 80.5 (C2'), 75.3 (C3'), 60.8 (C5'), 44.3 (C6'); 19…”

“…In recent years, several double-headed nucleoside designs have been presented in the literature. [7][8][9][10][11][12][13] Our previous work has shown that depending on the site of attachment, the additional nucleobase can be positioned in the minor groove, [14][15][16][17] the major groove, [18][19][20] or the center of a DNA duplex. [21][22][23] In the latter case, given that the additional nucleobase is linked through a methylene to the 2'-position of 2'-deoxyuridine or arabinouridine (Figure 1, U X ), the doubleheaded nucleotide has been shown to behave as a condensed dinucleotide.…”