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- Berner, Andreas, et al.
(författare)
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G4-ligand-conjugated oligonucleotides mediate selective binding and stabilization of individual G4 DNA structures
- 2023
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 146:10, s. 6926-6935
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Tidskriftsartikel (refereegranskat)abstract
- G-quadruplex (G4) DNA structures are prevalent secondary DNA structures implicated in fundamental cellular functions, such as replication and transcription. Furthermore, G4 structures are directly correlated to human diseases such as cancer and have been highlighted as promising therapeutic targets for their ability to regulate disease-causing genes, e.g., oncogenes. Small molecules that bind and stabilize these structures are thus valuable from a therapeutic perspective and helpful in studying the biological functions of the G4 structures. However, there are hundreds of thousands of G4 DNA motifs in the human genome, and a long-standing problem in the field is how to achieve specificity among these different G4 structures. Here, we developed a strategy to selectively target an individual G4 DNA structure. The strategy is based on a ligand that binds and stabilizes G4s without selectivity, conjugated to a guide oligonucleotide, that specifically directs the G4-Ligand-conjugated oligo (GL-O) to the single target G4 structure. By employing various biophysical and biochemical techniques, we show that the developed method enables the targeting of a unique, specific G4 structure without impacting other off-target G4 formations. Considering the vast amount of G4s in the human genome, this represents a promising strategy to study the presence and functions of individual G4s but may also hold potential as a future therapeutic modality.
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| 3. |
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| 4. |
- Gołębiewska, Justyna, et al.
(författare)
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Second generation of nucleotide analogues
- 2021
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Ingår i: Phosphorus Sulfur and Silicon and the Related Elements. - : Informa UK Limited. - 1042-6507 .- 1563-5325. ; 197:5-6, s. 511-514
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Tidskriftsartikel (refereegranskat)abstract
- The most common type of modification of a phosphorus center is the replacement of one or two non-bridging atoms of the phosphate group with different heteroatoms (e.g., sulfur, selenium) or groups of atoms (e.g., methyl, borane). Such compounds are referred to as the first generation of nucleotide analogues. We were interested in exploring the possibility of further functionalizing of the heteroatoms present in nucleoside phosphorothioates, phosphoroselenoate or boranephosphonates to create a second generation of nucleotide analogues with hopefully new biological properties. Here we report a preliminary account of our work on introducing additional modifications on the sulfur or selenium heteroatom of nucleotide analogues.
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