The contribution of thymine--thymine interactions to the stability of folded dimeric quadruplexes

Abstract

The loop of four thymines in the sodium form of the dimeric folded quadruplex [d(G3T4G3)]2 assumes a well-defined structure in which hydrogen bonding between the thymine bases appears to contribute to the stability and final conformation of the quadruplex. We have investigated the importance of the loop interactions by systematically replacing each thymine in the loop with a cytosine. The quadruplexes formed by d(G3CT3G3), d(G3TCT2G3), d(G3T2CTG3) and d(G3T3CG3) in the presence of 150 mM Na+ were studied by gel mobility, circular dichroism and 1H NMR spectroscopy. The major species formed by d(G3CT3G3), d(G3TCT2G3) and d(G3T3CG3) at 1 mM strand concentration at neutral pH is a dimeric folded quadruplex. d(G3T2CTG3) has anomalous behaviour and associates into a greater percentage of linear four-stranded quadruplex than the other three oligonucleotides at neutral pH and at the same concentration. The linear four-stranded quadruplex has a greater tendency to oligomerize to larger ill-defined structures, as demonstrated by broad 1H NMR resonances. At pH 4, when the cytosine is protonated, there is a greater tendency for each of the oligonucleotides to form some four-stranded linear quadruplex, except for d(G3T2CTG3), which has the reverse tendency. The experimental results are discussed in terms of hydrogen bonding within the thymine loop.

Structural characterization of ultra-stable higher-ordered aggregates generated by novel guanine-rich DNA sequences

“…Additionally, after quantitatively measuring the intensity of electrophoresis bands, d(G 11 T) could generated the clearest and most prominent ladder bands of low mobility among d(G11N) series, which was more evident in the original data. Intriguingly, the role of thymidine residues in the formation and stabilization of G-quadruplex structures have been reported for the different GROs (Balgurumoorthy et al, 1992;Keniry et al, 1997;Cheng and Van Dyke, 1997). The non-guanine bases in G-rich telomeric sequences are usually thymine residues with A G 1 1 T G 1 1 C G 1 1 A G 6 C G 5 G 6 A G 5 G 6 T G 5 G 3 G 6 G 9 G 1 2 G 2 0 G 1 1 G 1 2 G 1 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 * * * * * * * * * * * * T G 1 0 T p G 1 1 T T G 1 1 G 1 1 T 2 G 1 1 T 3 G 7 T G 9 T G 1 1 T G 1 3 T G 1 5 T A G 1 0 T C G 1 0 T G 1 1 T Table 1 and their formula is shown above each lane.…”

Synthesis and photochromic behavior of some azo-polysiloxanes modified with nucleobases or donor-acceptor groups

“…These re-organization phenomena are favored by the H-bond formation by the nucleobase with itself (between the nucleobase moieties). The possibility to form such H-bonds is a well known process, especially in the case of thymine that has a similar structure with uracil [21,22].…”

The 5′‐untranslated RNA of the human dhfr minor transcript alters transcription pre‐initiation complex assembly at the major (core) promoter

“…Thus, these quadruplex structures apparently contribute to the ability of the minor transcript 5 0 -UTR to sequester transcription factors. We suspect that the sequences naturally flanking the G-tracts within the minor transcript 5 0 -UTR help to define the structural characteristics of this particular quadruplex [Keniry et al, 1997;Smirnov and Shafer, 2000], and are likely responsible for the much greater selectivity of the minor transcript RNA for sequestration of transcription factors (Sp3 > Sp1 > z) compared with the G-tract oligonucleotides.…”