AMIDE-MODIFIED OLIGONUCLEOTIDES WITH PREORGANIZED BACKBONE AND FURANOSE RINGS - HIGHLY INCREASED THERMODYNAMIC STABILITY OF THE DUPLEXES FORMED WITH THEIR RNA AND DNA COMPLEMENTS

The amide backbone modification C3'-CH2-CONH-C5' has been further modi fied by introducing a methyl at C5', either in R or in S configuration . Only the S stereoisomer can adopt the required geometry to fit into a duplex with complementary RNA. Additional O-methyl groups at C2' of the furanose generate antisense oligonucleotides with considerably imp roved binding affinity to complementary RNA (Delta T-m up to 4.4 degre es C per modification).