The chemical end-ligation of homopyrimidine oligodeoxyribonucleotides within a DNA triple helix Original Research Article

The chemical end-ligation of homopyrimidine oligodeoxyribonucleotides within a DNA triple helix Original Research Article Pages 209-214 Tianhu Li, David S. Weinstein, K.C. Nicolaou Close preview | PDF (3573 K) | Related articles | Related reference work articles AbstractAbstract | ReferencesReferences Abstract Background: Triple-helical nucleic acids, first reported in the late 1950s, are receiving attention for their possible involvement in controlling gene expression. Certain sequences of DNA are believed to form local triple-helical structures (H-form DNA), although this has not been directly observed in vivo. Studies carried out in our laboratories have suggested that self-replicating oligonucleotides could have been involved in chemical evolution via triple-helical intermediates. In addition to self-replication mechanisms, elucidating processes for the nonenzymatic elongation of biologically relevant polymers remains an important challenge in understanding the origin of life. To this end, we have studied a novel ligation of oligodeoxyribonucleotides that lie within a triple helix. Results: The chemical end-ligation of homopyrimidine oligodeoxyribonucleotides on a triple helix is reported. This selective 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 the antiparallel oligopyrimidine strand. Conclusions: Double-helical homopurine/homopyrimidine DNA can serve as a template for the elongation of oligonucleotides in a manner that has not been described previously. The end-ligation of homopyrimidine oligomers, a nonenzymatic process, proceeds via a requisite triple-helical intermediate and constitutes an efficient and selective method for the template-directed elongation of nucleic acids. Such a process could conceivably have been involved in the elongation of primordial information-bearing biopolymers.