Template-directed oligonucleotide ligation on hydroxylapatite

Abstract

Bernal¹, and subsequently other authors², have suggested that the prebiotic synthesis of the precursors of biopolymers could have occurred on a solid surface such as that provided by clay or some other mineral. The separation of products from the other components of the reaction mixture in such a system is reminiscent of modern solid-phase synthesis of polypeptides and polynucleotides. One such scheme envisages that growing polymers were localized by adsorption to a mineral surface where an activating agent or activated monomers were supplied continuously or cyclically^3,4. We have been trying to test this scheme using reactions which we believe may be related to those that occurred during prebiotic evolution. We have already reported that oligonucleotides adsorbed onto hydroxylapatite provide suitable templates for the oligomerization of (guanosine 5′-phosphor)-2-methylimidazolide (2-MeImpG)^4–7. However, this is not a suitable test reaction, as 2-MeImpG oligomerization proceeds almost to completion in a single step. Here we report that a sequence of reactions in which initially formed oligo(G)s are reactivated by conversion to phosphorimidazolides in the presence of poly(C) and then allowed to ligate is ideal, in that repeated cycles can be carried out on the surface of hydroxylapatite, whereas in the liquid phase the cycle could be achieved only with considerable difficulty.