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Studies Towards Nucleic Acids at the Origins of Life

Colville, Ben W.F.; (2021) Studies Towards Nucleic Acids at the Origins of Life. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Nucleic acids are at the heart of extant biology and the structure of life’s original genetic polymer is still a question of debate. The RNA world theory proposes that RNA was the first nucleic acid employed as life’s genetic polymer due to its dual ability as informational storage (genotype) and primordial catalyst (phenotype). However, ribonucleotides are complex chemical structures, and simpler or more stable nucleic acids, such as threose nucleic acid (TNA) or DNA, can also carry genetic information. In principle, nucleic acids like TNA could have played a vital role in the origins of life but the advent of any genetic polymer requires synthesis of its monomers. This work demonstrates a high-yielding, stereo-, regio- and furanosyl-selective prebiotic synthesis of threo-cytidine, an essential component of TNA. This work uses key intermediates (aminooxazolines) and reactions previously exploited in the prebiotic synthesis of the canonical pyrimidine ribonucleoside cytidine. It avoids the low yielding glycosylations that have previously been demonstrated for constructing nucleic acids and utilises and efficient photochemical anomerization that is enabled by selective anhydronucleoside thiolysis. This work also demonstrates that erythro-specific 2',3'-cyclic phosphate synthesis provides a mechanism to photochemically select TNA cytidine and suggests that TNA may have coexisted with RNA during the emergence of life. This thesis also investigates whether DNA be delivered simultaneously with RNA, the co-emergence of both would further probe the place and importance of DNA at the origin of life. This work expands on previous work towards DNA and examines the role of irreversible thiol addition to anhydronucleosides as a route towards DNA precursors. Finally, the question of why the nucleobases present in extant biology (A, G, C, U/T) were chosen is addressed. This work explores the paradigm of UV stability as a selection pressure and the results contrast with current thinking that the purine nucleobases were chosen for their ability to resist degradation by UV-light.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Studies Towards Nucleic Acids at the Origins of Life
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10129094
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