Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.682242
Title: Dynamic-combinatorial approaches towards the non-enzymatic transcription of nucleic acids
Author: Wong, Raymond
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2006
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Abstract:
Recently developed in our laboratories are three systems to investigate non-enzymatic transcription of DNA/RNA. Firstly, a glyoxal/sec-amino monomer which polymerises to form a pyrrolidine-oligonucleotide mimic1 under reductive amination conditions. Secondly, an acetaldehyde/amino mono mer which polymerises to yield a novel pyrrolidine-amine oligonucleotide mimic and thirdly, a 1,4-dioxane-2,6-diol monomer which acts as a dialdehyde to produce a morpholino oligonucleotide mimic. All three systems will interact with the nucleic acid template in a reversible fashion, thus only the most thermodynamically stable products are amplified. The glyoxal and acetaldehyde monomers were a considerable synthetic challenge. Together the two thymidyl monomers were synthesised in 27 steps from trans-4-hydroxy-L-proline. Under physiological conditions the glyoxal is in the hydrated form which hinders iminium formation and the acetaldehyde monomer intramolecularly cyclises in preference to undergoing polymerisation. However, the 1,4-dioxane-2,6-diol (dialdehyde) can be synthesised in one step and initial results have demonstrated 100% fidelity in a non-enzymatic single nucleotide chain extension reaction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.682242  DOI: Not available
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