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Prebiotic assembly of nucleic acids


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Since the discovery of catalytic RNAs called ribozymes, there has been speculation that RNA was the first biopolymer responsible for the advent of life on earth. Life depends on the information storage provided by DNA and the biocatalysis provided by proteins. The RNA world hypothesis proposes that RNA fulfilled both of these functions in early life forms, acting both as a gene and an enzyme. However, efforts to demonstrate a prebiotically plausible synthesis of nucleic acids such as RNA have proven exceptionally challenging.One challenge of synthesizing RNA stems from the inability to find an efficient pathway to nucleoside synthesis, the monomer of nucleic acids. Termed the nucleoside problem, the canonical nucleobases guanine, adenine, cytosine, thymine, and uracil do not form a glycosidic linkage with ribose to a significant extent. In this thesis, work is presented showing the possibility that alternate sugars, such as ribulose, dried with adenine can form adenosine, albeit in trace amounts.Additionally, this thesis proposes a model for base-pair selection and nucleic acid polymerization. Since short nucleic acids, or oligonucleotides, have a persistence length of 2-4 nucleotides, oligonucleotides self-cyclize before linear polymerization. Intercalation increases the persistence length of oligonucleotides to ~100 nucleotides, mediating the polymerization of nucleic acids. Intercalators also select for specific base pairs to intercalate, mediating intercalation among base pairs that topologically fit the planar, aromatic face of the intercalator.



Undergraduate Research Option Theses - School of Chemistry and Biochemistry Undergraduate Research Option Theses -



Author: Chen, Michael C. - -

Source: https://smartech.gatech.edu/







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