DNA triplex formation of oligonucleotide analogs consisting of linker groups and octamer segments that have opposite sugar-phosphate backbone polarities

Biochemistry ◽  
1991 ◽  
Vol 30 (41) ◽  
pp. 9914-9921 ◽  
Author(s):  
Akira Ono ◽  
Ching Nien Chen ◽  
Lou Sing Kan
Keyword(s):  
Sugar Phosphate ◽  
Triplex Formation ◽  
Phosphate Backbone ◽  
Dna Triplex

The interaction of the 2′-OH group with the vicinal phosphate in ribonucleoside 3′-ethylphosphate drives the sugar-phosphate backbone into unique (S,ω−) conformational state

Tetrahedron ◽  
1995 ◽  
Vol 51 (43) ◽  
pp. 11775-11792 ◽  
Author(s):  
J. Plavec ◽  
C. Thibaudeau ◽  
G. Viswanadham ◽  
C. Sund ◽  
A. Sandström ◽  
...  
Keyword(s):  
Conformational State ◽  
Sugar Phosphate ◽  
Phosphate Backbone

scholarly journals Theoretical modelling of epigenetically modified DNA sequences

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 52 ◽  
Author(s):  
Alexandra Teresa Pires Carvalho ◽  
Maria Leonor Gouveia ◽  
Charan Raju Kanna ◽  
Sebastian K. T. S. Wärmländer ◽  
Jamie Platts ◽  
...  
Keyword(s):  
Molecular Mechanics ◽  
Dna Sequences ◽  
Base Pair ◽  
Density Functional ◽  
Epigenetic Modifications ◽  
Theoretical Modelling ◽  
Sugar Phosphate ◽  
Base Pairs ◽  
Phosphate Backbone ◽  
Modified Dna

We report herein a set of calculations designed to examine the effects of epigenetic modifications on the structure of DNA. The incorporation of methyl, hydroxymethyl, formyl and carboxy substituents at the 5-position of cytosine is shown to hardly affect the geometry of CG base pairs, but to result in rather larger changes to hydrogen-bond and stacking binding energies, as predicted by dispersion-corrected density functional theory (DFT) methods. The same modifications within double-stranded GCG and ACA trimers exhibit rather larger structural effects, when including the sugar-phosphate backbone as well as sodium counterions and implicit aqueous solvation. In particular, changes are observed in the buckle and propeller angles within base pairs and the slide and roll values of base pair steps, but these leave the overall helical shape of DNA essentially intact. The structures so obtained are useful as a benchmark of faster methods, including molecular mechanics (MM) and hybrid quantum mechanics/molecular mechanics (QM/MM) methods. We show that previously developed MM parameters satisfactorily reproduce the trimer structures, as do QM/MM calculations which treat bases with dispersion-corrected DFT and the sugar-phosphate backbone with AMBER. The latter are improved by inclusion of all six bases in the QM region, since a truncated model including only the central CG base pair in the QM region is considerably further from the DFT structure. This QM/MM method is then applied to a set of double-stranded DNA heptamers derived from a recent X-ray crystallographic study, whose size puts a DFT study beyond our current computational resources. These data show that still larger structural changes are observed than in base pairs or trimers, leading us to conclude that it is important to model epigenetic modifications within realistic molecular contexts.

Unlocked nucleic acids: implications of increased conformational flexibility for RNA/DNA triplex formation

2014 ◽  
Vol 464 (2) ◽  
pp. 203-211 ◽  
Author(s):  
Weronika Kotkowiak ◽  
Michał Kotkowiak ◽  
Ryszard Kierzek ◽  
Anna Pasternak
Keyword(s):  
Nucleic Acids ◽  
Conformational Flexibility ◽  
Hairpin Structure ◽  
Triplex Formation ◽  
Dna Triplex

UNA moieties within the TFO strongly destabilize triplexes. Introduction of UNA into specific positions in the hairpin structure is energetically favourable for triplex formation. UNA increases the resistance of the oligonucleotides to serum nucleases when incorporated at specific hairpin positions.

scholarly journals Inhibition of Interleukin-4- and CD40-induced IgE Germline Gene Promoter Activity by 2′-Aminoethoxy-modified Triplex-forming Oligonucleotides

2001 ◽  
Vol 276 (15) ◽  
pp. 11759-11765 ◽  
Author(s):  
Adrian M. Stütz ◽  
Jutta Hoeck ◽  
Francois Natt ◽  
Bernard Cuenoud ◽  
Maximilian Woisetschläger
Keyword(s):  
B Cells ◽  
Critical Role ◽  
Gene Promoter ◽  
Gene Induction ◽  
Modified Oligonucleotides ◽  
Germline Gene ◽  
Triplex Formation ◽  
Human B Cells ◽  
Dna Triplex

Elevated levels of IgE are intimately associated with a number of allergic diseases, such as allergic rhinitis or asthma. Therefore, prevention of IgE production in human B-cells represents an attractive therapeutic target. IL-4-induced IgE germline gene transcription represents a crucial early step during IgE isotype switch differentiation. Gene induction is orchestrated by the coordinated action of the transcription factors STAT6 (signal transducer and activator of transcription), NF-κB, PU.1, and C/EBP. This study shows that 2′-aminoethoxy-modified oligonucleotides, which partially overlap with the STAT6 and the adjacent PU.1/NF-κB binding site, inhibit DNA binding of all three proteins with high affinity in a dose- and time-dependent fashionin vitro. Loss of protein binding correlated strongly with increasing DNA triplex formation. Importantly, the oligomers also effectively displaced pre-bound recombinant NF-κB p50 from double-stranded DNAin vitro. Functionally, the oligonucleotides led to a selective inhibition of IL-4-induced reporter gene activity from a construct driven by the IgE germline gene promoter in human B-cells. These data confirm the critical role of this cytokine-responsive regulatory region in IgE germline gene induction and further support the concept of specific modulation of gene expression by DNA triplex formation induced with chemically modified oligonucleotides.

A Molecular Beacon Strategy for the Thermodynamic Characterization of Triplex DNA:  Triplex Formation at the Promoter Region of Cyclin D1†

Biochemistry ◽  
2001 ◽  
Vol 40 (31) ◽  
pp. 9387-9395 ◽  
Author(s):  
Thomas Antony ◽  
Thresia Thomas ◽  
Leonard H. Sigal ◽  
Akira Shirahata ◽  
T. J. Thomas
Keyword(s):  
Cyclin D1 ◽  
Promoter Region ◽  
Molecular Beacon ◽  
Triplex Dna ◽  
Thermodynamic Characterization ◽  
Triplex Formation ◽  
Dna Triplex
Sign in / Sign up

Export Citation Format

Share Document