Autocatalytic synthesis of a tetranucleotide analogue

Abstract

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.