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.
Department of Medicinal Chemistry, Isis Pharmaceuticals, 1891 Rutherford Road, Carlsbad, CA 92008, USA. pseth@isisph.com
Punit P
PP
Seth
Jinghua
J
Yu
Charles R
CR
Allerson
Andres
A
Berdeja
Eric E
EE
Swayze
D001483:Base Sequence; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D044366:Transition Temperature
D019086:Bridged Bicyclo Compounds, Heterocyclic; D009841:Oligonucleotides; C477371:locked nucleic acid