Hairpin and duplex formation of the DNA octamer d(m<sup>5</sup>C-G-m<sup>5</sup>C-G-T-G-m5C-G) in solution. An NMR study

Orbons, Leonard P. M.; Marel, G. A. Van Der; Boom, J. H. Van; Altona, C.

doi:10.1093/nar/14.10.4187

Cited by 59 publications

(48 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, such a thermodynamic profile is to be expected in light of the stable tandem sheared GA mismatch duplex formation in d(GCGAGC), which is known to give thermodynamic parameters just slightly lower than those for normal CG Watson-Crick base pairs. 28 In contrast, other known sheared mismatched pairs such as AA, AC, and GT 1,38,44,45 result in only minor contribution of the duplex form to the overall equilibrium in solution as evidenced from Table VII. Unfortunately, the thermodynamic analysis of d(GCGGGC) remains incomplete due to intermediate exchange being encountered on the NMR timescale, which is reversibly transformed to fast exchange at T [ 335 K. This suggests that the structure formed in solution from hexamer d(GCGGGC) features outstanding thermodynamic stability, higher by melting temperature T m than any other hexameric duplex from the d(GCXYGC) family of oligonucleotides (Table VII), indirectly suggesting the presence of a G-quadruplex structure in our hands.…”

Section: Thermodynamic Analysismentioning

confidence: 98%

“…Counter to this and for these ODNs, with the exception of d(GCGAGC), no sigmoidal-shaped temperature curves are observed, which are normally associated with duplex predominance in solution. It follows that the family of hexamers characterized by a mean diffusion coefficient of 28,29,38,39 Formally, this means that a d(GCGAGC) hairpin structure can exist in solution along with the duplex form. Although not evidenced in the NMR data from this work, the assumption about hairpin formation is in accordance with our molecular modeling study vide supra coupled with the well-known fact that DNA hairpins with loops bracketed by sheared GA mismatched base pairs are extraordinarily temperature stable.…”

Section: Thermodynamic Analysismentioning

confidence: 99%

See 1 more Smart Citation

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

et al. 2010

View full text Add to dashboard Cite

The entire family of noncomplementary hexamer oligodeoxyribonucleotides d(GCXYGC) (X and Y = A, G, C, or T) were assessed for topological indicators and equilibrium thermodynamics using a priori molecular modeling and solution phase NMR spectroscopy. Feasible modeled hairpin structures formed a basis from which solution structure and equilibria for each oligonucleotide were considered. ¹H and ³¹P variable temperature-dependent (VT) and concentration-dependent NMR data, NMR signal assignments, and diffusion parameters led to d(GCGAGC) and d(GCGGGC) being understood as exceptions within the family in terms of self-association and topological character. A mean diffusion coefficient D(298 K) = (2.0 ± 0.07) × 10⁻¹⁰ m² s⁻¹ was evaluated across all hexamers except for d(GCGAGC) (D(298 K) = 1.7 × 10⁻¹⁰ m² s⁻¹) and d(GCGGGC) (D(298 K) = 1.2 × 10⁻¹⁰ m² s⁻¹). Melting under VT analysis (T(m) = 323 K) combined with supporting NMR evidence confirmed d(GCGAGC) as the shortest tandem sheared GA mismatched duplex. Diffusion measurements were used to conclude that d(GCGGGC) preferentially exists as the shortest stable quadruplex structure. Thermodynamic analysis of all data led to the assertion that, with the exception of XY = GA and GG, the remaining noncomplementary oligonucleotides adopt equilibria between monomer and duplex, contributed largely by monomer random-coil forms. Contrastingly, d(GCGAGC) showed preference for tandem sheared GA mismatch duplex formation with an association constant K = 3.9 × 10⁵M⁻¹. No direct evidence was acquired for hairpin formation in any instance although its potential existence is considered possible for d(GCGAGC) on the basis of molecular modeling studies.

show abstract

Section: Thermodynamic Analysismentioning

confidence: 98%

Section: Thermodynamic Analysismentioning

confidence: 99%

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The -UNCG-loops are also highly abundant, as the -GNRA-loops in the aforementioned systems. In DNA studies, the choice of heteronucleotide loop sequences Sarma et al 1987;Hiroa et al 1989) was guided by the discovery of unexpectedly stable "minihairpins" (Orbons et al 1986) and by theoretical considerations that four-membered loops would be most stable and that stability would be increased by formation of a base pair between the first and the last base of the loop. In this situation it was expected that this base pair formation is favored with a pyrimidine at the 5'-and the complementary purine at the 3'-end of the loop Blommers et al 1989).…”

Section: Unusually Stable Hairpinsmentioning

confidence: 99%

The Hairpin Elements of Nucleic Acid Structure: DNA and RNA Folding

Hilbers

Heus

Dongen

et al. 1994

Nucleic Acids and Molecular Biology

View full text Add to dashboard Cite

“…More recent studies on DNA hairpins have taken advantage ofadvances in oligonucleotide synthesis to construct sequences that exclusively form hairpin structures under a given set of solution conditions. These studies are beginning to provide information on the structure, stability, and melting behavior of DNA hairpins (24)(25)(26)(27)(28)(29)(30)(31). However, most studies to date have been conducted on hairpin structures that exclusively contain thymidine residues in the nonbonded loop region.…”

mentioning

confidence: 99%

Influence of loop residues on the relative stabilities of DNA hairpin structures.

Senior

Jones

Breslauer

1988

Proc. Natl. Acad. Sci. U.S.A.

155

106

View full text Add to dashboard Cite

We have determined the relative stabilities and melting behaviors of DNA hairpin structures as a function of the nonbonded residues in the loop. The specific family of hairpin structures we investigated in this work is formed by the 16-mer sequence d[CGAACG(X)4CGTTCG], where X is deoxyadenosine, deoxycytidine, deoxyguanosine, or deoxythymidine. As shown below, this 16-mer can fold back on itself to form a family ofDNA hairpin structures that possess a common hexameric stem duplex and a nonbonded loop of 4 nucleotides. For the hairpin structures investigated in this work, we varied the loop composition from all purine residues to all pyrimidine residues. X CGAACG X GCTTGC X X We thermodynamically characterized the relative stabilities and melting profies of these hairpin structures by a combination of spectroscopic and calorimetric techniques. To establish a thermodynamic "baseline," we also conducted parallel studies on the isolated hexameric duplex d[(CGAACG)'(CG-TTCG)], which corresponds to the common stem duplex present in each hairpin structure. Our spectroscopic and calorimetric data reveal the following: (i) The hairpin structure with four dT residues in the loop exhibits the highest melting temperature, while the corresponding hairpin structure with four dA residues in the loop exhibits the lowest melting temperature. (i) The free energy data at 25°C reveal the following order of DNA hairpin stability for the four structures studied here: T loop > C loop > G loop > A loop. In other words, the pyrimidine-looped hairpins of four residues are more stable than the purine-looped hairpins. (iii) The loopdependent order of hairpin stability is paralleled by a similar trend in the calorimetrically determined transition enthalpies for hairpin disruption. Thus, the enhanced stability of the pyrimidine-looped hairpin structures relative to purine-looped hairpin structures is enthalpic in origin. To develop insight into the molecular basis for the thermodynamic differences, proton NMR spectroscopy was used to probe for structural disparities between the most stable hairpin structure (T loop) and the least stable hairpin structure (A loop). Two-dimensional nuclear Overhauser enhancement spectroscopy revealed connectivities between the residues in the stem duplexes of both hairpin structures that are consistent with B-form DNA. In addition, the nonbonded residues in both the T and A loops exhibited the same connectivity patterns. However, on the 5' side of the stem-loopjunction, the T-loop residue exhibited a connectivity with the adjacent base pair of the stem duplex that is not observed for the corresponding A-loop residue. This difference in connectivities at the stem-loop junction may provide a structural basis for our observation that the T-looped hairpin structure is more stable than the corresponding A-looped hairpin structure.DNA sequences capable of forming hairpin structures frequently are found near functional loci such as regulation and promotion sites (1-4) as well as within cruciform structures (5...

show abstract

Hairpin and duplex formation of the DNA octamer d(m⁵C-G-m⁵C-G-T-G-m5C-G) in solution. An NMR study

Abstract: The partly self-complementary DNA octamer d(m5C-G-m5C-G-T-G-m5C-G) was

Cited by 59 publications

References 16 publications

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

The Hairpin Elements of Nucleic Acid Structure: DNA and RNA Folding

Influence of loop residues on the relative stabilities of DNA hairpin structures.

Contact Info

Product

Resources

About

Hairpin and duplex formation of the DNA octamer d(m5C-G-m5C-G-T-G-m5C-G) in solution. An NMR study

Abstract: The partly self-complementary DNA octamer d(m5C-G-m5C-G-T-G-m5C-G) was

Cited by 59 publications

References 16 publications

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

The Hairpin Elements of Nucleic Acid Structure: DNA and RNA Folding

Influence of loop residues on the relative stabilities of DNA hairpin structures.

Contact Info

Product

Resources

About

Hairpin and duplex formation of the DNA octamer d(m⁵C-G-m⁵C-G-T-G-m5C-G) in solution. An NMR study