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Published September 1, 1989 | public
Journal Article

Recognition of Thymine Adenine Base Pairs by Guanine in a Pyrimidine Triple Helix Motif

Abstract

Oligonucleotide recognition offers a powerful chemical approach for the sequence-specific binding of double-helical DNA. In the pyrimidine-Hoogsteen model, a binding size of >15 homopurine base pairs affords >30 discrete sequence-specific hydrogen bonds to duplex DNA. Because pyrimidine oligonucleotides limit triple helix formation to homopurine tracts, it is desirable to determine whether oligonucleotides can be used to bind all four base pairs of DNA. A general solution would allow targeting of oligonucleotides (or their analogs) to any given sequence in the human genome. A study of 20 base triplets reveals that the triple helix can be extended from homopurine to mixed sequences. Guanine contained within a pyrimidine oligonucleotide specifically recognizes thymine.adenine base pairs in duplex DNA. Such specificity allows binding at mixed sites in DNA from simian virus 40 and human immunodeficiency virus.

Additional Information

© 1989 American Association for the Advancement of Science. 26 April 1989; accepted 7 July 1989. We thank the National Institutes of Health (GM-35724), the Office of Naval Research, and the Parsons Foundation for generous support. We thank S. Singleton for valuable assistance in model building, A. Frankel for a gift of pHIV-CAT, and T. Povsic for large-scale plasmid preparation.

Additional details

Created:
August 19, 2023
Modified:
October 20, 2023