P -Stereodefined phosphorothioate analogs of glycol nucleic acids-synthesis and structural properties

Enantiomerically pure, protected acyclic nucleosides of the GNA type (glycol nucleic acids) ( N'), obtained from ( )-(+)- and ( )-(-)-glycidols and the four canonical DNA nucleobases (Ade, Cyt, Gua and Thy), were transformed into 3'- -DMT-protected 2-thio-4,4-pentamethylene-1,3,2-oxathiaph...

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Bibliographic Details
Published in:RSC advances 2018, Vol.8 (44), p.24942-24952
Main Authors: Tomaszewska-Antczak, Agnieszka, Jastrzębska, Katarzyna, Maciaszek, Anna, Mikołajczyk, Barbara, Guga, Piotr
Format: Article
Language:English
Subjects:
Atomic properties
Chemistry
Configurations
Deoxyribonucleic acid
Dichroism
DNA
Monomers
Nucleic acids
Organic chemistry
Phosphorus
Silica gel
Silicon dioxide
Stereochemistry
Synthesis
Thermal dissociation
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Summary:Enantiomerically pure, protected acyclic nucleosides of the GNA type (glycol nucleic acids) ( N'), obtained from ( )-(+)- and ( )-(-)-glycidols and the four canonical DNA nucleobases (Ade, Cyt, Gua and Thy), were transformed into 3'- -DMT-protected 2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane derivatives (OTP- N') containing a second stereogenic center at the phosphorus atom. These monomers were chromatographically separated into -diastereoisomers, which were further used for the synthesis of -stereodefined "dinucleoside" phosphorothioates N T ( N = A, C, G, T). The absolute configuration at the phosphorus atom for all eight N T was established enzymatically and verified chemically, and correlated with chromatographic mobility of the OTP- N' monomers on silica gel. The N units (derived from ( )-(+)-glycidol) were introduced into self-complementary PS-(DNA/GNA) octamers of preselected, uniform absolute configuration at P-atoms. Thermal dissociation experiments showed that the thermodynamic stability of the duplexes depends on the stereochemistry of the phosphorus centers and relative arrangement of the N units in the oligonucleotide strands. These results correlate with the changes of conformation assessed from circular dichroism spectra.
ISSN:2046-2069
2046-2069
DOI:10.1039/c8ra05568h