Synthesis and biophysical characterization of R-6'-Me-α-L-LNA modified oligonucleotides

The synthesis and biophysical properties of R-6'-Me-α-L-LNA, which has a methyl group in the (R) configuration on the 2',4'-bridging substituent of α-L-LNA, is reported. The synthesis of the uracil nucleobase phosphoramidite was efficiently accomplished in 14 steps and 8 chromatographic purifications starting from a known sugar intermediate. Biophysical evaluation revealed that substitution along the edge of the major groove does not impair the high affinity duplex forming ability of α-L-LNA modified oligonucleotides.