Autocatalytic synthesis of a tetranucleotide analogue

As an approach to the study of the kind of chemical process that might have contributed to the origin of life, attempts have been made to develop purely chemical systems in which oligonucleotides self-replicate. Although preformed oligonucleotides have been shown to facilitate the formation of their complements from activated mononucleotides, only a restricted range of oligomers are efficient templates1 and it will clearly be difficult to find a pair of complementary oligomers each of which will facilitate the formation of the other2. Many of the difficulties facing the development of a self-replicating system could be overcome by using a pair of complementary substrate molecules that condense together more easily than ribonucleotides. It would also be helpful if each substrate molecule contained equal numbers of purine and pyrimidine bases as, otherwise, there is a tendency for purines to be over-represented in the products1. We have therefore explored the chemistry of 3'-amino-3'-deoxynucleotides3 and their dimers4. We report here that the tetranucleoside triphosphoramidate GNHpCNHpGNHpCN3 acts as a template to catalyse the condensation of GNHpCNH2 and pGNHpCN3, forming further molecules of the template. The system is therefore autocatalytic, and in accordance with elementary theory the amount of product made increases with the square root of the template concentration.