The chemical end-ligation of homopyrimidine oligodeoxyribonucleotides within a DNA triple helix.
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.
Li
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Department of Chemistry The Skaggs Institute for Chemical Biology The Scripps Research Institute 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Weinstein
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DS
Nicolaou
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K
D004247:DNA / Q000737:chemistry*; D004261:DNA Replication / Q000502:physiology; D007202:Indicators and Reagents; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013698:Templates, Genetic
D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D004247:DNA