Prebiotic Formation of Plausible Proto-Nucleosides: Investigations into the Origins of Nucleotides with Ribose and Pairing Bases
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Roche, Tyler Patrick
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Abstract
The question of the origin of life on Earth is of the most fundamental importance to modern biochemistry. Of the major molecular components of life, its genetic polymers, RNA and DNA, are perhaps the most salient targets for investigation as the products of chemical evolution. After the discovery of RNA’s ability to catalyze reactions, the RNA World Hypothesis was proposed, highlighting the potential importance of RNA in the origin of life. This hypothesis, which—in its more widely-accepted current form—states that RNA was the primary biopolymer to evolve at the outset of life’s origin, has been the guiding principle for a generation of prebiotic chemistry. Despite various challenges present in the prebiotic formation of the components required to form RNA, its synthesis under early-Earth conditions has remained a prized goal for many in the field. An alternative hypothesis—one in which RNA was not the first major prebiotic polymer—has been under recent investigation, and in this hypothesis, RNA represents the ultimate genetic polymer, one that is the product of chemical and biological evolution, through multiple stages, starting from a putative proto-RNA.
In this dissertation, I describe investigations into robust pathways for the formation of the sugar components of modern nucleic acids, and the ability of noncanonical nucleobases to react directly with these sugars to form nucleosides and nucleotides, the monomers of a potential proto-RNA. Probing further, I investigate the ability of these noncanonical nucleosides to form and pair simultaneously in a one-pot solution under prebiotic conditions.
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2022-12-15
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Dissertation