THE CHEMICAL END-LIGATION OF HOMOPYRIMIDINE OLIGODEOXYRIBONUCLEOTIDESWITHIN A DNA TRIPLE-HELIX

Background: Triple-helical nucleic acids, first reported in the late 1 950s, are receiving attention for their possible involvement in contro lling gene expression. Certain sequences of DNA are believed to form l ocal triple-helical structures (H-form DNA), although this has not bee n directly observed in vivo. Studies carried out in our laboratories h ave suggested that self-replicating oligonucleotides could have been i nvolved in chemical evolution via triple-helical intermediates. In add ition to self-replication mechanisms, elucidating processes for the no nenzymatic elongation of biologically relevant polymers remains an imp ortant challenge in understanding the origin of life. To this end, we have studied a novel ligation of oligodeoxyribonucleotides that lie wi thin a triple helix. Results: The chemical end-ligation of homopyrimid ine oligodeoxyribonucleotides on a triple helix is reported. This sele ctive process, induced by cyanoimidazole, is facilitated by a template effect of the DNA aggregate and occurs between the 3' end (hydroxyl) of the third minor-groove-bound strand and the 5' end (phosphate) of t he antiparallel oligopyrimidine strand, Conclusions: Double-helical ho mopurine/homopyrimidine DNA can serve as a template for the elongation of oligonucleotides in a manner that has not been described previousl y. The end-ligation of homopyrimidine oligomers, a nonenzymatic proces s, proceeds via a requisite triple-helical intermediate and constitute s an efficient and selective method for the template-directed elongati on of nucleic acids, Such a process could conceivably have been involv ed in the elongation of primordial information-bearing biopolymers.