Stable triplex formation using the strong stacking effect of consecutive thionucleoside moieties

Abstract

In this study, it was found that the arrangement of consecutive thiocarbonyl groups of s(2)T and m(5)s(2)C remarkably stabilized the pre-protonated form of the triplex, and that the stabilization of the pre-protonated form increased the pKa value of a cytosine derivative in the triplex.

Synthesis and triplex-forming properties of oligonucleotides capable of recognizing corresponding DNA duplexes containing four base pairs

“…Scheme 1 shows the synthesis of 2’-OMe g C s phosphoramidite unit 2 . 2’-OMe s T phosphoramidite unit was converted to compound 6 by using phosphoryl chloride and then 1, 2, 4-triazole and introduction of a 2-aminoethylamino group into the 4-position of the pyrimidine ( 19 , 24 ) was carried out to obtain compound 7 . 2’-OMe g C s phosphoramidite unit 2 was synthesized by treating compound 7 with S -methylthiourea derivative 8 in 68% isolated yield from compound 5 (3 steps, Scheme 1 ).…”

“…For example, TFOs containing LNAs/BNAs ( 13 ) and 5-propynylpyrimidines ( 17 ) more strongly bind to targeted DNA duplexes than unmodified TFOs. A recent study conducted by us yielded the interesting result that the strong stacking effect of thiocarbonyl groups of 2’-OMe-2-thiothymidine ( 2’-OMe s T; Figure 1a ) ( 19 ) and 2’-OMe-8-thioadenosine ( 2’-OMe s A; Figure 1b ) ( 19 , 20 ) can increase the binding affinities of TFOs.…”

Facile Access to 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′,5′‐Dideoxyribonucleosides via Stable Disulfide Intermediates

“…Incorporation of a thiol function in nucleos(t)ides or oligonucleotides has led to a variety of analogs possessing interesting biological properties (Acevedo-Acevedo et al, 2011;Ohkubo et al, 2011;Fauster et al, 2012;Kikuchi et al, 2013;Kojima et al, 2013;Devi et al, 2014;Lebars et al, 2014;Thottassery et al, 2014). Additionally, oligodeoxynucleotides containing 5 -S-(4,4 -dimethoxytrityl)-2 ,5 -dideoxyribonucleoside monomers have been reported to undergo site-specific cleavage, and have therefore been explored for the detection and construction of DNA arrays (Jahn-Hofmann and Engels, 2004).…”

Tuning the selectivity of triplex DNA receptors

“…During filtration, free triplex receptors and receptor-ligand complexes remained on the membrane, whereas unbound ligands passed through the membrane. 11,13 Therefore substitution of cytosine with 5m2s C on the antiparallel homopyrimidine region increased the binding affinities for guanosine and inosine. The dissociation constants were calculated according to the total ligand concentration, the total receptor concentration, and the unbound ligand concentration (ESI †).…”

“…11 However, a free guanosine, which as a ligand is not constrained by the phosphate backbone, may bind to the triplex cavity in a flipped mode (Scheme 1c). It was reported that 5-methyl-2-thiocytosine ( 5m2S C) specifically paired with hypoxanthine favorably over guanine in a duplex DNA.…”