ArticleMolecular therapy. Nucleic acids2022
Antisense oligonucleotide gapmers containing phosphoryl guanidine groups reverse MDR1-mediated multiple drug resistance of tumor cells.
Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 32 citations in OpenAlex.
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- In Vivo Interactions of Nucleic Acid Nanostructures With Cells.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Synthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction.International journal of molecular sciences · 2024Article
- Chemical strategies for antisense antibiotics.Chemical Society reviews · 2024Review
- Amphiphilic Oligonucleotide Derivatives-Promising Tools for Therapeutics.Pharmaceutics · 2024Review
- Advancing cancer treatments: The role of oligonucleotide-based therapies in driving progress.Molecular therapy. Nucleic acids · 2024Review
- Unveiling the intricacy of gapmer oligonucleotides through advanced tandem mass spectrometry approaches and scan accumulation for 2DMS.The Analyst · 2024Article
- Current status and trends in small nucleic acid drug development: Leading the future.Acta pharmaceutica Sinica. B · 2024Review
- A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position.International journal of molecular sciences · 2024Article
- Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides.Molecules (Basel, Switzerland) · 2024Article
- G-Quadruplexes in the Regulation of Viral Gene Expressions and Their Impacts on Controlling Infection.Pathogens (Basel, Switzerland) · 2024Review
- Precision RNA base editing with engineered and endogenous effectors.Nature biotechnology · 2023Review
- Fork- and Comb-like Lipophilic Structures: Different Chemical Approaches to the Synthesis of Oligonucleotides with Multiple Dodecyl Residues.International journal of molecular sciences · 2023Article
- Switchable targeting of solid tumors by BsCAR T cells.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Towards Personalized Allele-Specific Antisense Oligonucleotide Therapies for Toxic Gain-of-Function Neurodegenerative Diseases.Pharmaceutics · 2022Review
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11 authors at 3 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Antisense gapmer oligonucleotides containing phosphoryl guanidine (PG) groups, e.g., 1,3-dimethylimidazolidin-2-imine, at three to five internucleotidic positions adjacent to the 3' and 5' ends were prepared via the Staudinger chemistry, which is compatible with conditions of standard automated solid-phase phosphoramidite synthesis for phosphodiester and, notably, phosphorothioate linkages, and allows one to design a variety of gapmeric structures with alternating linkages, and deoxyribose or 2'-O-methylribose backbone. PG modifications increased nuclease resistance in serum-containing medium for more than 21 days. Replacing two internucleotidic phosphates by PG groups in phosphorothioate-modified oligonucleotides did not decrease their cellular uptake in the absence of lipid carriers. Increasing the number of PG groups from two to seven per oligonucleotide reduced their ability to enter the cells in the carrier-free mode. Cationic liposomes provided similar delivery efficiency of both partially PG-modified and unmodified oligonucleotides. PG-gapmers were designed containing three to four PG groups at both wings and a central "window" of seven deoxynucleotides with either phosphodiester or phosphorothioate linkages targeted to MDR1 mRNA providing multiple drug resistance of tumor cells. Gapmers efficiently silenced MDR1 mRNA and restored the sensitivity of tumor cells to chemotherapeutics. Thus, PG-gapmers can be considered as novel, promising types of antisense oligonucleotides for targeting biologically relevant RNAs.
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