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Unusual Thermal Stability of RNA/[R_P-PS]-DNA/RNA Triplexes Containing a Homopurine DNA Strand

Piotr Guga ^*, Magorzata Boczkowska ^*, Magdalena Janicka ^*, Anna Maciaszek ^*, Sawomir Kuberski  and Wojciech J. Stec ^*

^* Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, ód, Poland; and Faculty of Process and Environmental Engineering, Technical University of ód, ód, Poland

Correspondence: Address reprint requests to Prof. Dr. Wojciech J. Stec, Tel.: 48-42-6819744; Fax: 48-42-6815483; E-mail: wjstec{at}bio.cbmm.lodz.pl.

Homopurine deoxyribonucleoside phosphorothioates, as short as hexanucleotides and possessing all internucleotide linkages of R_P configuration, form a triple helix with two RNA or 2'-OMe-RNA strands, with Watson-Crick and Hoogsteen complementarity. Melting temperature and fluorescence quenching experiments strongly suggest that the Hoogsteen RNA strand is parallel to the homopurine [R_P-PS]-oligomer. Remarkably, these triplexes are thermally more stable than complexes formed by unmodified homopurine DNA molecules of the same sequence. The triplexes formed by phosphorothioate DNA dodecamers containing 4–6 dG residues are thermally stable at pH 7.4, although their stability increases significantly at pH 5.3. FTIR measurements suggest participation of the C²-carbonyl group of the pyrimidines in the stabilization of the triplex structure. Formation of triple-helix complexes with exogenously delivered PS-oligos may become useful for the reduction of RNA accessibility in vivo and, hence, selective suppression/inhibition of the translation process.

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				P. Guga, M. Janicka, A. Maciaszek, B. Rebowska, and G. Nowak Hoogsteen-Paired Homopurine [RP-PS]-DNA and Homopyrimidine RNA Strands Form a Thermally Stable Parallel Duplex Biophys. J., November 15, 2007; 93(10): 3567 - 3574. [Abstract] [Full Text] [PDF]