Template-directed synthesis of high molecular weight polynucleotide analogues

Abstract

A GREAT deal is known about the structures of nucleic acids and the mechanisms involved in nucleic acid replication. This relatively new knowledge has led a number of authors to speculate that other linear heteropolymers might be able to serve as carriers of genetic information. A number of polynucleotide analogues have been synthesised by chemical or enzymatic methods^1–7 and one of them has been used as a template for RNA polymerase⁴. Two studies, in particular, have some relationship to the present work. 3′–5′-Linked polynucleotides derived from 2′-amino-2′-deoxynucleoside 5′-phosphates have been synthesised enzymatically⁷. Letsinger et al.^5,6 reported the chemical and enzymatic formation of polydeoxyribonucleotides containing N^5′–O^3′-phosphoramidate linkages. Here we discuss nucleic acid analogues derived from 2′-amino-2′-deoxynucleotides that we believe may be capable of non-enzymatic replication, and describe some experimental results which, although they are far from establishing the principle of self-replication, do show that it is possible to synthesise fairly long oligomers on templates in aqueous solution.