Incorporation of 2'-deoxy-6-thioguanosine into G-rich oligodeoxyribonucleotides inhibits G-tetrad formation and facilitates triplex formation.
An efficient and expeditious method for the synthesis of S6-(cyanoethyl)-N2-isobutyryl (or trifluoroacetyl)-2'-deoxy-6-thioguanosine (7 and 2) from 2'-deoxyguanosine (G) has been developed. Compound 7 has been incorporated into several G-rich triple-helix-forming oligonucleotides (TFOs) using solid-support, phosphoramidite chemistry. The purified oligonucleotides containing 2'-deoxy-6-thioguanosine (S6-dG) residues in the place of G have been characterized by nucleoside composition analysis. These modified TFOs have been shown to be stable in aqueous, as well as buffered, solutions normally used to assay triple-helix formation. It has also been demonstrated that partial incorporation of S6-dG is effective in inhibiting the formation of G tetrads in G-rich oligodeoxyribonucleotides, thus facilitating triple-helix formation in potassium-containing buffers.
Rao
T S
TS
Triplex Pharmaceutical Corporation, The Woodlands, Texas 77380.
Durland
R H
RH
Seth
D M
DM
Myrick
M A
MA
Bodepudi
V
V
Revankar
G R
GR
D001483:Base Sequence; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013872:Thionucleosides / Q000737:chemistry*
D009838:Oligodeoxyribonucleotides; D013872:Thionucleosides; C010438:beta-2'-deoxythioguanosine; D003849:Deoxyguanosine