Issue 41, 2022

Synthesis and hybridizing properties of P-stereodefined chimeric [PS]-{DNA:RNA} and [PS]-{DNA:(2′-OMe)-RNA} oligomers

Abstract

Oxathiaphospholane derivatives of 2′-OMe-ribonucleosides and 2′-O-TBDMS-ribonucleosides (MN-OTP and TN-OTP, respectively; nucleobase protected) were synthesized and separated into pure P-diastereomers. X-ray analysis showed the RP absolute configuration of the phosphorus atom in the fast-eluting diastereomer of TA-OTP. The fast- and slow-eluting P-diastereomers of MN-OTP and TN-OTP were used in the solid-phase synthesis of phosphorothioate dinucleotides (MNPST and NPST, respectively), which were subsequently hydrolyzed with RP-selective phosphodiesterase svPDE and SP-selective nuclease P1 to determine the absolute configuration of the phosphorus atoms. P-Stereodefined phosphorothioate ([PS]) 10-mer chimeric oligomers [PS]-{DNA:(2′-OMe)-RNA} and isosequential [PS]-{DNA:RNA} containing two MNPS or NPS units were synthesized. Melting experiments performed for their complexes with Watson–Crick paired DNA matrix showed that MNPS or NPS units decrease the thermal stability of the duplexes (ΔTm = −0.5 ÷ −5.5 °C per modification) regardless of the absolute configuration of the P-atoms. When the (2′-OMe)-RNA matrix was used an increase in Tm was noted in all cases (ΔTm = +1 ÷ +7 °C per modification). The changes in thermal stability of the duplexes formed by [PS]-chimeras with DNA and (2′-OMe)-RNA matrices do not correlate with the absolute configuration of the phosphorus atoms.

Graphical abstract: Synthesis and hybridizing properties of P-stereodefined chimeric [PS]-{DNA:RNA} and [PS]-{DNA:(2′-OMe)-RNA} oligomers

Supplementary files

Article information

Article type
Paper
Submitted
04 aug 2022
Accepted
08 sep 2022
First published
21 sep 2022
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2022,12, 26815-26824

Synthesis and hybridizing properties of P-stereodefined chimeric [PS]-{DNA:RNA} and [PS]-{DNA:(2′-OMe)-RNA} oligomers

K. Jastrzębska, A. Maciaszek, R. Dolot, A. Tomaszewska-Antczak, B. Mikołajczyk and P. Guga, RSC Adv., 2022, 12, 26815 DOI: 10.1039/D2RA04855H

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