NMR studies on truncated sequences of human telomeric DNA: observation of a novel A-tetrad

Abstract

The structure of the telomeric DNA has been a subject of extensive investigation in recent years due to the realization that it has important functional roles to play in vivo and the observations that truncated telomeric sequences exhibit a great variety of 3D structures in aqueous solutions. In this context, we describe here NMR structural studies on two truncated human telomeric DNA sequences, d-AG(3)T and d-TAG(3)T in solutions containing K(+)ions. The G(3)stretches in both the oligonucleotides were seen to form parallel-stranded quadruplexes. However, the AG(3)segment as a whole, had different structural characteristics. The structure of d-AG(3)T revealed the formation of a novel A-tetrad, which was not seen in d-TAG(3)T. The A's in the tetrad had syn glycosidic conformation as opposed to the anti conformation of the G's in the G-tetrads. The A-tetrad stacked well over the adjacent G-tetrad and the twist angle at this step was smaller in d-AG(3)T than in d-TAG(3)T. These observations are expected to be significant from the point of view of structural diversity and recognition in telomeres.

G‐Quadruplexes: Targets in Anticancer Drug Design

“…The number of slowly exchanging imino protons gives information about strand stoichiometry, the number of G-quartets, and the symmetry of the quadruplex structure. [123,124] The range of resonance frequencies indicates the presence of Watson-Crick base pairs, Hoogsteen-bonded imino protons, hydrogen-bonded amino protons, and exchange-protected imino protons from unpaired residues. In general, imino proton chemical shifts < 12.5 ppm are indicative of Watson-Crick base pairs (NH···H hydrogen bonds).…”

Adenine versus guanine quartets in aqueous solution: dispersion-corrected DFT study on the differences in π-stacking and hydrogen-bonding behavior

“…The adenine quartets have been observed experimentally in a planar configuration [4][5][6][7], and we examine whether these quartets remain in a planar configuration when the stabilization by the guanine quartets is not present. Finally, we test the applicability of the widely used B3LYP functional for these quartets in the different symmetries and we show that the neglect of the dispersion correction will even lead to erroneous conclusions.…”

Quadruplexes of human telomere DNA analogs designed to contain G:A:G:A, G:G:A:A, and A:A:A:A tetrads

“…16 Adenine was found among the most deleterious substitution in the structure built from four 5 0 -dTAG 3 T strands: no T m value could even be determined for it. With longer strands the parallel quadruplex became more stable: with 5 0 -dTAG 4 T-s only a strong destabilization was described, 17 and a relatively stable A-tetrad was observed by NMR for the 4-stranded structure consisting of 5 0 -dTTAG 3 T strands with anti-N-glycosidic torsion angles and N 6 HÀ ÀN 1 H-bonds.…”