Binding of T and T analogs to CG base pairs in antiparallel triplexes

The goal of this study was to address antiparallel triplex formation at duplex targets that do not conform to a strict oligopurine·oligopyrimidine motif. We focused on the ability of natural bases and base analogs incorporated into oligonucleotide third strands to bind to so-called CG inversions. Th...

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Bibliographic Details
Published in:Nucleic acids research 1994-08, Vol.22 (15), p.3233-3240
Main Authors: Durland, Ross H., Rao, T.Sudhakar, Revankar, Ganapathi R., Tinsley, John H., Myrick, Melissa A., Seth, Dale M., Rayford, Jamie, Singh, Pradeep, Jayaraman, Krishna
Format: Article
Language:English
Subjects:
Antineoplastic agents
Base Composition
Base Sequence
Biological and medical sciences
Cytosine - metabolism
Drug Stability
General aspects
Guanine - metabolism
Medical sciences
Molecular Sequence Data
Molecular Structure
Oligonucleotides - chemistry
Oligonucleotides - metabolism
Oxygen - chemistry
Pharmacology. Drug treatments
Structure-Activity Relationship
Thymidine - chemistry
Thymidine - metabolism
Thymine - analogs & derivatives
Thymine - metabolism
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Summary:The goal of this study was to address antiparallel triplex formation at duplex targets that do not conform to a strict oligopurine·oligopyrimidine motif. We focused on the ability of natural bases and base analogs incorporated into oligonucleotide third strands to bind to so-called CG inversions. These are sites where a cytosine base is present in an otherwise purine-rich strand of a duplex target. Using a 26-base-triplet test system, we found that of the standard bases, only thymine (T) shows substantial binding to CG inversions. This is qualitatively similar to the report of Beal and Dervan [Science (1991), 251, 1360–1363]. Binding to CG inversions was only slightly weaker than binding to AT base pairs. Binding of T to CG inversions was also evaluated in two other sequences, with qualitatively similar results. Six different analogs of thymine were also tested for binding to CG inversions and AT base pairs. Significant changes in affinity were observed. In particular, 5-fluoro-2′-deoxyuridine was found to increase affinity for CG inversions as well as for AT base pairs. Studies with oligonucleotides containing pyridin-2-one or pyridin-4-one suggest that thymine O4 plays a critical role in the T-CG interaction. Possible models to account for these observations are discussed.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/22.15.3233