Nucleic Acids Research, Vol 24, Issue 6 1136-1143, Copyright © 1996 by Oxford University Press
T de Bizemont, G Duval-Valentin, JS Sun, E Bisagni, T Garestier and C Helene
Triple helix formation requires a polypurine- polypyrimidine sequence in
the target DNA. Recent works have shown that this constraint can be
circumvented by using alternate strand triplex-forming oligonucleotides. We
have previously demonstrated that (T,G)-containing triplex- forming
oligonucleotides may adopt a parallel or an antiparallel orientation with
respect to an oligopurine target, depending upon the sequence and, in
particular, upon the number of 5'- GpT-3' and 5'-TpG-3' steps [Sun et al.
(1991) C.R. Acad. Sci. Paris Ser III, 313, 585-590]. A single
(T,G)-containing oligonucleotide can therefore interact with two
oligopurine stretches which alternate on the two strands of the target DNA.
The (T,G) switch oligonucleotide contains a 5'-part targeted to one of the
oligopurine sequences in a parallel orientation followed by a 3'-part that
adopts an antiparallel orientation with respect to the second oligopurine
sequence. We show that a limitation to the stability of such a triplex may
arise from the instability of the antiparallel part, composed of
reverse-Hoogsteen C.GxG and T.AxT base triplets. Using DNase I footprinting
and ultraviolet absorption experiments, we report that a
benzo[e]pyridoindole derivative [(3-methoxy- 7H-8-methyl-11-[(3'-amino-
propyl) amino] benzo[e]pyrido [4,3-b]indole (BePI)], a drug interacting
more tightly with a triplex than with a duplex DNA, strongly stabilizes
triplexes with reverse-Hoogsteen C.GxG and T.AxT triplets thus allowing a
stabilization of the triplex-forming switch (T,G) oligonucleotide on
alternating oligopurine- oligopyrimidine 5'-(Pu)14(Py)14-3' duplex
sequences. These results lead to an extension of the range of
oligonucleotide sequences for alternate strand recognition of duplex DNA.
ARTICLES
Alternate strand recognition of double-helical DNA by (T,G)-containing oligonucleotides in the presence of a triple helix-specific ligand
Laboratoire de Biophysique, CNRS URA 481, INSERM U 201, Paris, France.
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