Evaluation of Novel Third-Strand Bases for the Recognition of a C⋅G Base Pair in the Parallel DNA Triple-Helical Binding Motif

Abstract

We describe the synthesis and the incorporation into oligonucleotides of the novel nucleoside building blocks 9, 10, and 16, carrying purine-like double H-bond-acceptor bases. These base-modified nucleosides were conceived to recognize selectively a cytosine ¥ guanine (C ¥ G) inversion site within a homopurine ¥ homopyrimidine DNA duplex, when constituent of a DNA third strand designed to bind in the parallel binding motif. While building block 16 turned out to be incompatible with standard oligonucleotide-synthesis conditions, UV/ triplex melting experiments with third-strand 15-mers containing b-d-nucleoside 6 (from 9) showed that recognition of the four natural Watson-Crick base pairs follows the order G ¥ C % C ¥ G > A ¥ T > T ¥ A. The recognition is sequence-context sensitive, and G ¥ C or C ¥ G recognition does not involve protonated species of b-d-nucleoside 6. The data obtained fit (but do not prove) a structural model for C ¥ G recognition via one conventional and one CÀH ¥¥¥ O H-bond. The unexpected G ¥ C recognition is best explained by third-strand base intercalation. A comparison of the triplex binding properties of these new bases with those of 4deoxothymine (5-methylpyrimidine-2(1H)-one, 4 H T), previously shown to be C ¥ G selective but energetically weak, is also described.

Design, Synthesis, and Biological Evaluation of 2-Nitroimidazopyrazin-one/-es with Antitubercular and Antiparasitic Activity

“…34 Second, microwave heating (μW 120 °C) of 19a–f , 19k–l , 19n , and 19t under acidic conditions afforded the bicyclic products 17a–f , 17k–l , 17n , and 17t . This synthesis was based on the preparation of des-nitro-imidazopyrazinone 20a , as previously described by Prévot and Leumann; 35 however, microwave heating at higher temperatures and for shorter periods than conventional reflux facilitated analogue generation for both steps. Second, inclusion of a cosolvent (aq 2 M HCl/1,4-dioxane 1:1) was necessary to solubilize the secondary amide starting material and achieve conversion to the desired products 17b–f , 17k–l , 17n , and 17t .…”

“…This has previously been observed for this class of compounds and is proposed to be due to protonation of the imidazopyrazinone core. 13 35 7-Benzylimidazo[1,2-a]pyrazin-8(7H)-one; 20b. To a stirred suspension of compound 23b (120 mg, 0.378 mmol) in H 2 O (20 vol.)…”

Towards the Sequence‐Selective Recognition of Double‐Stranded DNA Containing Pyrimidine‐Purine Interruptions by Triplex‐Forming Oligonucleotides

“…[44] The Q nucleobase shown in Figure 12 was also designed and evaluated. [47] It recognized a GC base pair rather than a CG base pair in triplex DNA.…”

Targeting DNA base pair mismatch with artificial nucleobases. Advances and perspectives in triple helix strategy

“…5). 45 This latter appeared to be less selective than 5-methylpyrimidin-2-one and did not distinguish between CG and GC base pairs. Furthermore, the triplex stability was found to be highly dependent on the nature of the neighbour bases around the target site.…”