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Prebiotic Chemistry and the Origin of Life

The University of Manchester, Manchester, UK
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  • Chemistry
  • Medicine


The Sutherland group recently demonstrated the prebiotic synthesis of activated pyrimidine ribonucleotides as their 2',3'-cyclic phosphates, and these species are candidates for oligomerisation to RNA. These species hydrolyse to the corresponding 2'- and 3'-monophosphates and there is a need to discover prebiotically plausible ways to re-activate to the cyclic material. Previous methods have suffered from poor yields and/or derivatization of the nucleobase. This study describes a new multicomponent reaction that achieves highly efficient nucleotide activation and at the same time produces amino acid derivatives, also of importance in the origin of life. This reactivity is then further developed and utilised in the prebiotic synthesis of derivatives of glyceric acid 2- and 3-phosphate, used in the glycolysis pathway in contemporary biochemistry.Aminoacyl-RNA trimers are central to the RNA:coded peptides theory by Sutherland, whereby RNA replication and coded peptide synthesis are proposed to have emerged together in the origin of life. The aminoacylation of an RNA trimer is therefore investigated, again using a multicomponent reaction.With the prebiotic synthesis and re-activation of nucleoside-2',3'-cyclic phosphates shown, the oligomerisation of these species is now a major goal. The dry-state oligomerisation of these species using ethanolamine as catalyst is discussed. Key ethanolamine-adduct intermediates are identified, and the preference for the formation of natural [3'-5'] linkages produced by this type of oligomerisation is rationalised.The compartmentalisation of a primitive replicating genetic system is considered an important stage in the origin of life in order to overcome the high dilution of the oceans. Previous studies have focussed on long chain carboxylic acids for this purpose but these are unstable to the conditions required for RNA folding and catalysis, and only form bilayer vesicles at a specific pH. The final chapter investigates the prebiotic synthesis of a simple phospholipid amphiphile that has the potential to form more suitable lipid vesicles.

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