Effect of the Incorporation of 2′-Deoxy-8-(Hydroxyl)Adenosine on the Stability of Quadruplexes Formed by Modified Human Telomeric DNA

Petraccone, Luigi; Duro, Ida; Erra, Eva; Randazzo, Antonio; Virno, Ada; Giancola, Concetta

doi:10.1080/15257770701490597

Cited by 5 publications

(4 citation statements)

References 7 publications

(10 reference statements)

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“…8-Oxo- 2′ -deoxyadenosine (o 8 dA) . The first study with 7,8-dihydro-8-oxo-2′-deoxyadenosine (8-oxodA or o 8 dA, Figure 15 , 2 ), another oxidative natural base lesion, was carried out by Esposito et al [ 290 ] and Petraccone et al [ 291 ] using the tetramolecular parallel GQ DNA models of [AGGGT] 4 and [TAGGGT] 4 . All the modified oligonucleotides formed the same parallel-type tetramolecular GQs as the unmodified two oligonucleotides did.…”

Section: Natural Base Lesions and Epigenetic Modifications In Gq Dmentioning

confidence: 99%

“…The o 8 dA substituting for dA nucleotides in both structures decreased the thermostability of the parent GQs by 14°C and 8°C, respectively, according to absorption-based T m measurement, and the drastic negative effects were supposed to originate from the formation of the o 8 dA-tetrads [ 290 ]. Calorimetry, however, provided different results: the [AGGGT] 4 GQ was not destabilized by the analog, formulated as 8-hydroxy-dA, oh 8 dA [ 291 ].…”

Section: Natural Base Lesions and Epigenetic Modifications In Gq Dmentioning

confidence: 99%

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In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

Sági¹

2017

Journal of Nucleic Acids

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Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferred syn or anti N-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring the in vitro action of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events.

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Section: Natural Base Lesions and Epigenetic Modifications In Gq Dmentioning

confidence: 99%

Section: Natural Base Lesions and Epigenetic Modifications In Gq Dmentioning

confidence: 99%

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

Sági¹

2017

Journal of Nucleic Acids

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“…35 There have been an increasing number of thermodynamic and kinetic experiments that were performed to unravel the stability and specificity of small ligands and the G-quadruplexes. [36][37][38][39][40][41][42] In addition, a singlemolecule-based method was applied to study the G-quadruplexpyridostatin interactions. 43 Recently, metadynamics simulations have been used to study the mechanistic insights of ligand binding to the G-quadruplex.…”

Section: A Introductionmentioning

confidence: 99%

The molecular mechanism of ligand unbinding from the human telomeric G-quadruplex by steered molecular dynamics and umbrella sampling simulations

Zhou

Yang

Sheu

2015

Phys. Chem. Chem. Phys.

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G-quadruplexes are attractive drug targets in cancer therapy. Understanding the mechanisms of the binding-unbinding processes involving biomolecules and molecular recognition is essential for designing new drugs of G-quadruplexes. We performed steered molecular dynamics and umbrella sampling simulations to investigate the molecular mechanism and kinetics of ligand unbinding processes of the basket, propeller and hybrid G-quadruplex structures. Our studies of the ligand charge effect showed that Coulomb interaction plays a significant role in stabilizing the G-quadruplex structure in the unbinding process. The free energy profiles were carried out and the free energy changes associated with the unbinding process were computed quantitatively, whereas these results could help to identify accessible binding sites and transient interactions. The dynamics of the hydration shell water molecules around the G-quadruplex exhibits an abnormal Brownian motion, and the thickness and free energy of the hydration shell were estimated. A two-step relaxation scheme was theoretically developed to describe the kinetic reaction of BMVC and G-quadruplex interactions. Our computed results fall in a reasonable range of experimental data. The present investigation could be helpful in the structure-based drug design.

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“…17,18 Incorporation of adenosine analogs has been reported to result in changed conformations in tetrameric quadruplexes. 19 Incorporation of ribonucleosides into DNA quadruplexes has been shown to restrict the possible conformations to parallel strand orientations. The likely reason for this observation is the preference of the anti-conformation of the ribonucleoside glycosidic bond.…”

mentioning

confidence: 99%

Redesigned tetrads with altered hydrogen bonding patterns enable programming of quadruplex topologies

Benz

Hartig

2008

Chem. Commun.

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Effect of the Incorporation of 2′-Deoxy-8-(Hydroxyl)Adenosine on the Stability of Quadruplexes Formed by Modified Human Telomeric DNA

Cited by 5 publications

References 7 publications

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

The molecular mechanism of ligand unbinding from the human telomeric G-quadruplex by steered molecular dynamics and umbrella sampling simulations

Redesigned tetrads with altered hydrogen bonding patterns enable programming of quadruplex topologies

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