Synthesis of 1′-phenyl-2′-OMe ribose analogues connecting the thymine base at the 1′ position through a flexible linker for the formation of a stable anti-parallel triplex DNA

Enhancement of TFO Triplex Formation by Conjugation with Pyrene <i>via</i> Click Chemistry

“…(1S,2R,3R,4R)-1-(2-Formylethyl)-2-Omethyl-1-phenyl-3,5-O-tetraisopropyldisiloxyribose (11) 14) was synthesized as described in our previous paper. The aldehyde group was converted to the alkyne unit using Ohira-Bestmann reagents, followed by treatment with tetrabutylammonium fluoride (TBAF) to obtain the diol compound (12).…”

“…(1S,2R,3R,4R)-2-O-Methyl-1-phenyl-1-propargylribose (12) Under an Ar atmosphere, the solution of compound 11 (600 mg, 1.18 mmol) 14) in dry methanol (3.0 mL) was added to a mixture of dimethyl(1-diazo-2-oxopropyl) phosphonate (670 mg, 3.55 mmol) and potassium carbonate (280 mg, 2.00 mmol) in dry methanol (6.0 mL) at 0°C. After stirring for 3 h at the same temperature, the reaction was quenched with water and extracted with diethylether.…”

“…Surprisingly, no triplex band was observed for TFO(ethyl(T)), therefore, we thought that the 14-mer TFO with the WNA derivative [12][13][14][15][16][17][18] would not form the triplex DNA for the region including one CG site. The results of the gel-shift assay and the K s value demonstrated that pyrene contributed to the stability of triplex formation with target duplex DNA.…”

“…To overcome the drawback of sequence specificity and enable the use of TFOs as genomic research tools, researchers have attempted to develop artificial nucleoside analogues able to recognize the CG or TA sites with high selectivity and/or stability. [6][7][8][9][10][11] We developed W-shaped nucleoside analogues (WNAs) able to recognize the TA site with high selectivity, [12][13][14][15][16][17][18] and demonstrated that the antigene TFO containing three WNA-βTs exerted an anti-proliferative effect on living cells. 19) Molecules with non-selective stabilizing effects would represent a powerful tool to promote triplex formation.…”

Development of Novel Functional Molecules Targeting DNA and RNA

“…38,39) Substitution at the benzene unit of WNA-βT was able to partially solve the problem of sequence dependency. [40][41][42][43][44][45][46] To demonstrate the utility of WNA-βT for the antigene inhibition of gene expression, the WNA-βT was incorporated into amino-modified TFOs containing the promoter region of the Bcl2 and the survivin gene. 47) Bcl2 and survivin gene products are inhibitors of apoptosis and are overexpressed in a variety of tumors.…”