scholarly journals Development of Gene‐Targeted Polypyridyl Triplex‐Forming Oligonucleotide Hybrids

ChemBioChem ◽  
2020 ◽  
Vol 21 (24) ◽  
pp. 3563-3574 ◽  
Author(s):  
Nicolò Zuin Fantoni ◽  
Bríonna McGorman ◽  
Zara Molphy ◽  
Daniel Singleton ◽  
Sarah Walsh ◽  
...  
Keyword(s):  
Triplex Forming Oligonucleotide

Antigene and Antiproliferative Effects of Triplex-Forming Oligonucleotide (TFO) Targeted on hmgb1 Gene in Human Hepatoma Cells

2020 ◽  
Vol 20 (16) ◽  
pp. 1943-1955
Author(s):  
Neelam Lohani ◽  
Moganty R. Rajeswari
Keyword(s):  
Apoptotic Cell ◽  
Isothermal Calorimetry ◽  
High Mobility ◽  
Rational Drug Design ◽  
Human Hepatoma Cells ◽  
Aberrant Expression ◽  
Bioinformatic Tools ◽  
Hmgb1 Expression ◽  
Dna Triplex ◽  
Triplex Forming Oligonucleotide

Background: The high mobility group box 1 (hmgb1) is one of the frequently over-expressed genes whose aberrant expression is reported in a number of human cancers. Various strategies are underway to inhibit hmgb1 expression in cancer cells having considerable therapeutic value. Objective: The present work involves selective transcriptional inhibition of the hmgb1 gene using selective DNA triplex structure-based gene technology. Here, the promoter region of the hmgb1 gene at position (-183 to -165) from the transcription start site as a target was selected using bioinformatic tools. Methods: The DNA triplex formation by the DNA of the target gene and TFO was confirmed using UV absorption spectroscopy, Circular Dichroism, and Isothermal Calorimetry. Results: Treatment of HepG2 cell with specific Triplex-forming Oligonucleotide significantly downregulated HMGB1 expression level at mRNA and protein levels by 50%, while the classical anticancer drugs, actinomycin/ adriamycin as positive controls showed 65% and the combination of TFO and drug decreased by 70%. The anti-proliferative effects of TFO correlated well with the fact of accumulation of cells in the Go phase and apoptotic cell death. Further, the binding of anti-cancer drugs to hmgb1 is stronger in DNA triplex state as compared to hmgb1 alone, suggesting the combination therapy as a better option. Conclusion: Therefore, the ability of hmgb1 targeted triplex-forming oligonucleotide in combination with triplex selective anticancer drug holds promise in the treatment of malignancies associated with hmgb1 overexpression. The result obtained may open up new vistas to provide a basis for the rational drug design and searching for high-affinity ligands with a high triplex selectivity.

scholarly journals Reconstructing the Free Energy Profiles Describing the Switching Mechanism of a pH-Dependent DNA Nanodevice from ABMD Simulations

2021 ◽  
Vol 11 (9) ◽  
pp. 4052
Author(s):  
Alice Romeo ◽  
Mattia Falconi ◽  
Alessandro Desideri ◽  
Federico Iacovelli
Keyword(s):  
Free Energy ◽  
Double Helix ◽  
Minimum Energy ◽  
Switching Mechanism ◽  
Linker Length ◽  
Energy Profiles ◽  
Functional Dna ◽  
Triplex Forming Oligonucleotide ◽  
Dynamics Simulations ◽  
Free Energy Profiles

The pH-responsive behavior of six triple-helix DNA nanoswitches, differing in the number of protonation centers (two or four) and in the length of the linker (5, 15 or 25 bases), connecting the double-helical region to the single-strand triplex-forming region, was characterized at the atomistic level through Adaptively Biased Molecular Dynamics simulations. The reconstruction of the free energy profiles of triplex-forming oligonucleotide unbinding from the double helix identified a different minimum energy path for the three diprotic nanoswitches, depending on the length of the connecting linker and leading to a different per-base unbinding profile. The same analyses carried out on the tetraprotic switches indicated that, in the presence of four protonation centers, the unbinding process occurs independently of the linker length. The simulation data provide an atomistic explanation for previously published experimental results showing, only in the diprotic switch, a two unit increase in the pKa switching mechanism decreasing the linker length from 25 to 5 bases, endorsing the validity of computational methods for the design and refinement of functional DNA nanodevices.

Synthesis, Incorporation into Triplex-Forming Oligonucleotide, and Binding Properties of a Novel 2‘-Deoxy-C-Nucleoside Featuring a 6-(Thiazolyl-5)benzimidazole Nucleobase

2002 ◽  
Vol 4 (24) ◽  
pp. 4209-4212 ◽  
Author(s):  
Dominique Guianvarc'h ◽  
Jean-Louis Fourrey ◽  
Rosalie Maurisse ◽  
Jian-Sheng Sun ◽  
Rachid Benhida
Keyword(s):  
Binding Properties ◽  
Triplex Forming Oligonucleotide

Strand Breaks in Whole Plasmid DNA Produced by the Decay of125I in a Triplex-Forming Oligonucleotide

2001 ◽  
Vol 156 (2) ◽  
pp. 158-166 ◽  
Author(s):  
Irina V. Panyutin ◽  
Andrew N. Luu ◽  
Igor G. Panyutin ◽  
Ronald D. Neumann
Keyword(s):  
Plasmid Dna ◽  
Strand Breaks ◽  
Triplex Forming Oligonucleotide

scholarly journals Triplex-forming oligonucleotide-orthophenanthroline conjugates for efficient targeted genome modification

2008 ◽  
Vol 105 (28) ◽  
pp. 9576-9581 ◽  
Author(s):  
F. Cannata ◽  
E. Brunet ◽  
L. Perrouault ◽  
V. Roig ◽  
S. Ait-Si-Ali ◽  
...  
Keyword(s):  
Genome Modification ◽  
Targeted Genome Modification ◽  
Triplex Forming Oligonucleotide
Sign in / Sign up

Export Citation Format

Share Document