Details of Grant 

EPSRC Reference:	GR/S56610/01
Title:	Potentially Prebiotic Synthesis & Replication of RNA
Principal Investigator:	Sutherland, Professor J
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Chemistry
Organisation:	University of Manchester, The
Scheme:	Standard Research (Pre-FEC)
Starts:	01 March 2004	Ends:	28 February 2007	Value (£):	417,974
EPSRC Research Topic Classifications:	Biological & Medicinal Chem.
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:
Summary on Grant Application Form
Previous approaches to the potentially prebiotic synthesis of RNA have assumed the synthetic sequence; sugar, nucleoside, nucleotide, RNA. Despite forty-odd years of research, this sequence has not been demonstrated, major problems being; the derivation of ribose, attachment of the bases to ribose, regioselective phosphorylation, phosphate activation and activated nucleotide polymerisation. We have now demonstrated a synthesis of pyrimidine nucleotides in which the base is sequentially assembled on a sugar phosphate template via an anhydronucleotide intermediate. We now seek to extend these findings which suggest an alternative synthetic sequence to RNA; phosphate diester, cyclic trimeric sugar phosphate, cyclic trinucleotide, linear anhydro-terminated trinucleotide, RNA. We propose to investigate this sequence using conventional synthetic chemistry to prepare intermediates and standards for the each of the various 'prebiotic' steps. We will prepare several simple phosphodiesters and examine aldol polymerisation to oligomers. Model oligomers and more realistic cyclic trimers will be synthesised and subjected to the pyrimidine base assembly conditions. Similar 'anhydro' routes to purine nucleotides will be sought. Finally we will prepare anhydro-terminated linear trimers and determine whether templated ligation can take place by nucleophilic substitution chemistry.
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Organisation Website:	http://www.man.ac.uk