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Science 1 September 1989:
Vol. 245. no. 4921, pp. 967 - 971
DOI: 10.1126/science.2549639
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Articles

Science, Vol 245, Issue 4921, 967-971
Copyright © 1989 by American Association for the Advancement of Science

articles

Recognition of thymine adenine.base pairs by guanine in a pyrimidine triple helix motif

LC Griffin and PB Dervan

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.

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 greater than 15 homopurine base pairs affords greater than 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.


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