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Graphical summary. Credit score: Journal of the American Chemical Society (2024). DOI: 10.1021/jacs.3c14626
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Graphical summary. Credit score: Journal of the American Chemical Society (2024). DOI: 10.1021/jacs.3c14626
For the primary time, scientists from the College of Cologne (UoC) have developed synthetic nucleotides, the constructing blocks of DNA, with a number of extra properties within the laboratory, which may very well be used as synthetic nucleic acids for therapeutic purposes.
DNA carries the genetic data of all dwelling organisms and consists of solely 4 totally different constructing blocks, the nucleotides. Nucleotides are composed of three distinctive elements: a sugar molecule, a phosphate group, and one of many 4 nucleobases adenine, thymine, guanine, and cytosine.
The nucleotides are lined up tens of millions of occasions and kind the DNA double helix, just like a spiral staircase. Scientists from the UoC’s Division of Chemistry have now proven that the construction of nucleotides may be modified to a terrific extent within the laboratory. The researchers developed so-called threofuranosyl nucleic acid (TNA) with a brand new, extra base pair.
These are the primary steps on the best way to totally synthetic nucleic acids with enhanced chemical functionalities. The examine “Increasing the Horizon of the Xeno Nucleic Acid Area: Threose Nucleic Acids with Elevated Info Storage’ was revealed within the Journal of the American Chemical Society.
Synthetic nucleic acids differ in construction from their originals. These modifications have an effect on their stability and performance. “Our threofuranosyl nucleic acid is extra secure than the naturally occurring nucleic acids DNA and RNA, which brings many benefits for future therapeutic use,” mentioned Professor Dr. Stephanie Kath-Schorr.
For the examine, the 5-carbon sugar deoxyribose, which types the spine of DNA, was changed by a 4-carbon sugar. As well as, the variety of nucleobases was elevated from 4 to 6. By exchanging the sugar, the TNA shouldn’t be acknowledged by the cell’s personal degradation enzymes. This has been an issue with nucleic acid-based therapeutics, as synthetically produced RNA that’s launched right into a cell is quickly degraded and loses its impact.
The introduction of TNAs into cells that stay undetected may now keep the impact for longer. “As well as, the built-in unnatural base pair allows various binding choices to focus on molecules within the cell,” added Hannah Depmeier, lead writer of the examine. Kath-Schorr is for certain that such a operate can be utilized particularly within the improvement of recent aptamers, quick DNA or RNA sequences, which can be utilized for the focused management of mobile mechanisms.
TNAs may be used for the focused transport of medication to particular organs within the physique (focused drug supply) in addition to in diagnostics; they may be helpful for the popularity of viral proteins or biomarkers.
Extra data:
Hannah Depmeier et al, Increasing the Horizon of the Xeno Nucleic Acid Area: Threose Nucleic Acids with Elevated Info Storage, Journal of the American Chemical Society (2024). DOI: 10.1021/jacs.3c14626
Journal data:
Journal of the American Chemical Society