The DNA carries the genetic information of all living organisms and consists of only 4 different constructing blocks, the nucleotides. Nucleotides are composed of three distinctive parts: a sugar molecule, a phosphate group and one among the 4 nucleobases adenine, thymine, guanine and cytosine. The nucleotides are lined up thousands and thousands of times and form the DNA double helix, just like a spiral staircase. Scientists from the UoC’s Department of Chemistry have now shown that the structure of nucleotides may be modified to an important extent within the laboratory.
The researchers developed so-called threofuranosyl nucleic acid (TNA) with a brand new, additional base pair. These are the primary steps on the method to fully artificial nucleic acids with enhanced chemical functionalities. The study ‘Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage’ was published within the Journal of the American Chemical Society.
Artificial nucleic acids differ in structure from their originals. These changes affect their stability and performance. “Our threofuranosyl nucleic acid is more stable than the naturally occurring nucleic acids DNA and RNA, which brings many benefits for future therapeutic use,” said Professor Dr Stephanie Kath-Schorr. For the study, the 5-carbon sugar deoxyribose, which forms the backbone in DNA, was replaced by a 4-carbon sugar. As well as, the variety of nucleobases was increased from 4 to 6. By exchanging the sugar, the TNA shouldn’t be recognized by the cell’s own degradation enzymes. This has been an issue with nucleic acid-based therapeutics, as synthetically produced RNA that’s introduced right into a cell is rapidly degraded and loses its effect. The introduction of TNAs into cells that remain undetected could now maintain the effect for longer.
“As well as, the built-in unnatural base pair enables alternative binding options to focus on molecules within the cell,” added Hannah Depmeier, lead writer of the study. Kath-Schorr is for certain that such a function may be used particularly in the event of recent aptamers, short DNA or RNA sequences, which may be used for the targeted control of cellular mechanisms. TNAs is also used for the targeted transport of medicine to specific organs within the body (targeted drug delivery) in addition to in diagnostics; they may even be useful for the popularity of viral proteins or biomarkers.
