Depmeier, Hannah ORCID: 0000-0001-9825-3134 (2024). Artificial nucleic acids with enhanced functionalities. PhD thesis, Universität zu Köln.
PDF (PhD thesis)
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Abstract
To date, a plethora of artificial nucleic acid analogs with enhanced functional properties have been described in the literature. However, most of the currently described artificial nucleic acids comprise a modification in only one structural element of the tripartite structure of nucleic acids, which is comprised of a phosphate backbone, a sugar moiety, and a nucleobase. This work explores the enzymatic synthesis of a novel artificial nucleic acid variant with modifications in the sugar and the nucleobase moieties. Therefore, the nuclease-resistant alpha-L-threofuranosyl nucleic acid (TNA) was combined with the unnatural hydrophobic base pair TPT3:NaM. In this context, the alpha-L-threofuranosyl NaM triphosphate and the TNA nucleotides bearing the canonical nucleobases were synthesized. The enzymatic incorporation of the highly modified nucleotide building blocks bearing the unnatural TPT3 and NaM nucleobases into TNA was investigated using different TNA-compatible polymerases. The enzymatic synthesis of TPT3-modified TNA was successfully achieved, whereas the preparation of NaM-modified TNA presented greater challenges. This study marks the first enzymatic synthesis of TNA with an expanded genetic alphabet (exTNA), opening promising opportunities in nucleic acid therapeutics, particularly for the selection of nuclease-resistant, high-affinity aptamers.
Item Type: | Thesis (PhD thesis) | ||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-736070 | ||||||||||||||||||||||
Date: | 2024 | ||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||
Faculty: | Faculty of Mathematics and Natural Sciences | ||||||||||||||||||||||
Divisions: | Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Organic Chemistry | ||||||||||||||||||||||
Subjects: | Natural sciences and mathematics Chemistry and allied sciences Life sciences |
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Date of oral exam: | 9 September 2024 | ||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/73607 |
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