ArticleBiophysical journal2007
Phosphorothioate oligonucleotides block the VDAC channel.
Article in Biophysical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Phosphorothioate backbone modification of oligodeoxynucleotides induces TLR9-independent lung epithelial antimicrobial responses.American journal of respiratory cell and molecular biology · 2026Article
- Solute Transport through Mitochondrial Porins In Vitro and In Vivo.Biomolecules · 2024Review
- Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight.International journal of molecular sciences · 2023Review
- Chemistry of Therapeutic Oligonucleotides That Drives Interactions with Biomolecules.Pharmaceutics · 2022Review
- Structure and Gating Behavior of the Human Integral Membrane Protein VDAC1 in a Lipid Bilayer.Journal of the American Chemical Society · 2022Article
- Noncoding RNA therapeutics - challenges and potential solutions.Nature reviews. Drug discovery · 2021Review
- Structure, gating and interactions of the voltage-dependent anion channel.European biophysics journal : EBJ · 2021Review
- Pharmacological modulation of mitochondrial ion channels.British journal of pharmacology · 2019Review
- Functional Reconstitution of Membrane Proteins Derived From Eukaryotic Cell-Free Systems.Frontiers in pharmacology · 2019Article
- VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis.Frontiers in chemistry · 2018Review
- Voltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-Cancer Therapeutics.Frontiers in oncology · 2017Review
- News about VDAC1 in Hypoxia.Frontiers in oncology · 2016Article
- Combined effect of G3139 and TSPO ligands on Ca(2+)-induced permeability transition in rat brain mitochondria.Archives of biochemistry and biophysics · 2015Article
- Tubulin tail sequences and post-translational modifications regulate closure of mitochondrial voltage-dependent anion channel (VDAC).The Journal of biological chemistry · 2015Article
- Chemically defined polyethylene glycol siRNA conjugates with enhanced gene silencing effect.Bioorganic & medicinal chemistry · 2014Article
- VDAC1-based peptides: novel pro-apoptotic agents and potential therapeutics for B-cell chronic lymphocytic leukemia.Cell death & disease · 2013Article
- Small peptides against the mutant SOD1/Bcl-2 toxic mitochondrial complex restore mitochondrial function and cell viability in mutant SOD1-mediated ALS.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Mitochondrial permeability transition pore as a selective target for anti-cancer therapy.Frontiers in oncology · 2013Article
- VDAC inhibition by tubulin and its physiological implications.Biochimica et biophysica acta · 2012Review
- Does the voltage dependent anion channel modulate cardiac ischemia-reperfusion injury?Biochimica et biophysica acta · 2012Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proapoptotic phosphorothioate oligonucleotides such as G3139 (an 18-mer) induce Bcl-2-independent apoptosis, perhaps partly via direct interaction with VDAC and reduction of metabolite flow across the mitochondrial outer membrane. Here, we analyzed the interactions at the molecular level. Ten micromolar G3139 induces rapid flickering of the VDAC conductance and, occasionally, a complete conductance drop. These phenomena occur only when VDAC is in the "open" conformation and therefore are consistent with pore blockage rather than VDAC closure. Blockage occurs preferentially from one side of the VDAC channel. It depends linearly on the [G3139] and is voltage-dependent with an effective valence of -3. The kinetics indicate at least a partial entry of G3139 into VDAC, forming an unstable bound state, which is responsible for the rapid flickering (approximately 0.1 ms). Subsequently, a long-lived blocked state is formed. An 8-mer phosphorothioate, polydeoxythymidine, induces partial blockage of VDAC and a change in selectivity from favoring anions to favoring cations. Thus, the oligonucleotide is close to the ion stream. The phosphodiester congener of G3139 is ineffective at the concentrations used, excluding a general polyanion effect. This shows the importance of sulfur atoms. The results are consistent with a binding-induced blockage rather than a permeation block.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.