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

Abstract:

: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 quantitatively 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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Durland RH,Rao TS,Revankar GR,Tinsley JH,Myrick MA,Seth DM,Rayford J,Singh P,Jayaraman K

doi

10.1093/nar/22.15.3233

subject

Has Abstract

pub_date

1994-08-11 00:00:00

pages

3233-40

issue

15

eissn

0305-1048

issn

1362-4962

journal_volume

22

pub_type

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