The Extension of a DNA Double Helix by an Additional Watson–Crick Base Pair on the Same Backbone

Abstract

Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand.

Base‐Pairing Properties of Double‐Headed Nucleotides

“…The C2′-exo position of β-nucleosides emerges as the most reasonable site for introducing an additional base and enable dual Watson-Crick contacts. 18 In our preceding studies, we have gauged the potential of three designs (double-headed β-ᴅ-ribosides, 25 β-ᴅ-deoxyribosides 26,27 and β-ᴅarabinosides; 24,28,29 see Figure 1) in terms of their synthetic feasibility and dinucleotide potential. For convenience, uracil has invariably been used as the C1′-linked base.…”

“…Contrarily, the deoxyribo structure displayed potent recognition of complementary sequences indicative of dinucleotide behavior. 26,27 This highlighted the importance of using a shorter linker and/or the importance of the sugar puckering. Nevertheless, this building block could only be obtained following a long synthetic route with poor yielding steps, which foiled its development.…”

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.…”

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

“…[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. In practice, it can form two sets of Watson-Crick base pairs with two individual nucleotides of the opposite strand: one through its 1'-base to give a 1'•1' base pair, and another through its 2'-base to give a 2'•1' base pair.…”

“…In recent years, several double‐headed nucleoside designs have been presented in the literature [7–13] . Our previous work has shown that depending on the site of attachment, the additional nucleobase can be positioned in the minor groove, [14–17] the major groove, [18–20] or the center of a DNA duplex [21–23] . 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 double‐headed nucleotide has been shown to behave as a condensed dinucleotide.…”