The antisense strategy has gained wide acceptance as a promising drug development concept. Antisense drugs hybridize with selected complementary sequences in a highly specific manner. However, as a main prerequisite for extensive therapeutic use of this new class of drugs, selected structural modifications are required to adjust pharmacokinetic and pharmacodynamic behavior. In continuation of our earlier investigations on 2′- O -modified oligonucleotides (Cotten, M., Oberhauser, B., Brunar, H., Holzner, A., Issakides, G., Noe, C.R., Schaffer, G., Wagner, E., Birnstiel, M.L., 1991. 2′- O -methyl, 2′- O -ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. Nucleic Acids Res. 19, 2629–2635; Wagner, E., Oberhauser, B., Holzner, A., Brunar, H., Issakides, G., Schaffner, G., Cotten, M., Knollmüller, M., Noe, C.R., 1991. A simple procedure for the preparation of protected 2′- O -methyl or 2′- O -ethyl ribonucleoside-3′- O -phosphoramidites. Nucleic Acids Res. 19, 5965–5971) further series of modified oligonucleotides containing different modified 2′- O -adenosines have been synthesized. On the one hand linear alkyl moieties of increasing length, on the other hand oxyethylene moieties of corresponding length were introduced at the 2′- O -position of adenosine. Following another approach a cationic charge was introduced by insertion of an aminohexylmodification at the 2′- O -position of adenosine (Brunar, H., Haberhauer, G., Werner, D., Noe, C.R., 1994. 2′- O -Modified oligonucleotides: Synthesis and biophysical analysis. Eur. J. Pharm. Sci. 2, 150). Molecule dynamics simulations had shown that this cationic modification upon duplex formation leads to both intra- and interstrand interactions. To determine the influence of the different modifications, such as cationic charge, alkyl chainlength and introduction of oxygen into the chain, on duplex stability melting temperatures were measured by recording circular dichroism versus temperature.