D. S. Novopashinaa, 1, A. N. Sinyakova, V. A. Ryabinina, L. Perrouaultb,
C. Giovannangelib, A. G. Venyaminovaa, and A. S. Boutorineb
a Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS,
pr. Lavrentieva 8, Novosibirsk, 630090 Russia
b Muséum National d’Histoire Naturelle (MNHN), CNRS UMR 7196, INSERM U565, 57,
rue Cuvier, BP 26, 75231, Paris, cedex 05 France.
Received February 29, 2012; in final form, May 1, 2012.
Abstract—Triplex forming 3'-protected pyrimidine oligo(2'-O-methylribonucleotides) containing minor
groove binders (MGB) and triplex specific intercalator, benzoindoloquinoline (BIQ), at the 5'-terminus were
synthesized. The resulting conjugates formed stable complexes with a target dsDNA due to the simultaneous
binding to the minor and major grooves and BIQ intercalation. The dissociation constants and the thermal sta-
bility were evaluated for the conjugate complexes with the model dsDNA corresponding to the polypurine tract
(PPT) of the nef and pol genes from the HIV proviral genome. The conjugation of oligo(2'-O-methylribonucle-
otides) with MGB and BIQ was shown to increase the stability of the triple complexes with dsDNA at pH 7.2
and 37C. Moreover, the intercalator accelerates the process of the complex formation. The dose-dependent
arrest of the in vitro transcription was demonstrated when a 780-bp DNA fragment containing the polypurine
tract was transcribed under the control of T7 promoter in the presence of different concentrations of conjugates
of oligo(2'-O-methylribonucleotides) containing MGB and BIQ.
Keywords: oligo(2'-O-methylribonucleotides), conjugates, minor groove binder, intercalator, DNA triple helix,
inhibition of in vitro transcription
DOI: 10.1134/S1068162013010081
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