- Evaluation of novel third-strand bases for the recognition of a C·G base pair in the parallel DNA triple-helical binding motif
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We describe the synthesis and the incorporation into oligonucleotides of the novel nucleoside building blocks 9, 10, and 16, carrying purine-like double H-bond-acceptor bases. These base-modified nucleosides were conceived to recognize selectively a cytosine · guanine (C·G) inversion site within a homopurine · homopyrimidine duplex, when constituent of a DNA third strand designed to bind in the parallel binding motif. While building block 16 turned out to be incompatible with standard oligonucleotide-synthesis conditions, UV/triplex melting experiments with third-strand 15-mers containing β-D-nucleoside 6 (from 9) showed that recognition of the four natural Watson-Crick base pairs follows the order G·C ? C·G > A· T> T·A. The recognition is sequence-context sensitive, and G·C or C·G recognition does not involve protonated species of β-D-nucleoside 6. The data obtained fit (but do not prove) a structural model for C · G recognition via one conventional and one C - H··· O H-bond. The unexpected G · C recognition is best explained by third-strand base intercalation. A comparison of the triplex binding properties of these new bases with those of 4-deoxothymine (5-methylpyrimidine-2(1H)-one, 4HT), previously shown to be C·G selective but energetically weak, is also described.
- Prevot, Isabelle,Leumann, Christian J.
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p. 502 - 515
(2007/10/03)
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