We have found that an activated derivative of guanylic acid in which the phosphate group is converted to a 2-Me Imidazole derivative (2-MeImpG) undergoes very efficient regiospecific polymerization on a poly(C) template to give natural 3'-5'-linked oligoguanylic acids with chain lengths up to 30 or higher. Furthermore, templates containing C and one or more additional bases direct the synthesis of complementary oligomers. CCGCC for example directs the synthesis of GGCGG in up to 20% yield and from 2-MeImpG and 2-MeImpC. We plan to extend these studies with the intention of developing an RNA polymerase model that will enable us to use as wide a range of oligomers as possible as templates to direct complementary synthesis. Our long range goal is the development of a non-enzymatic replicating system. In addition to these extensions of our previous work, we hope to initiate four new areas of research:- (1) We will attach polycations such as oligoarginine to the 3'-terminus of templates in such a way as to force the correct initiation of synthesis. (2) We will use short oligonucleotide initiators to analyze the effect of different steps in the reaction on overall rates and efficiencies of the reactions. (3) We will use """"""""sliding"""""""" to bring about template synthesis on oligomers with a repeating sequence. If we are successful, it will be possible to achieve template-directed synthesis on a double-helical template, without needing to separate the strands. (4) We will investigate peptide catalysts of the template-directed reactions of dGTP.
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