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This is particularly important because considerable confusion has arisen concerning the potential utility of phosphorothioate oligonucleotides for selected therapeutic purposes deriving from unsophisticated interpretation of toxicological data. 2 mg/kg over 2 hr) FIGURE 2 Plasma concentrations of ISIS 2302 at which various activities are observed. These concentrations are determined by extracting plasma and analyzing by capillary gel electrophoresis and represent intact ISIS 2302. 30 Stanley T.
In this class of oligonucleotides, one of the oxygen atoms in the phosphate group is replaced with a sulfur. The resulting compound is negatively charged, as is a chiral phosphodiester, but much more resistant to nucleases (Cohen, 1993). B. Hybridization The hybridization of phosphorothioate oligonucleotides to DNA and RNA has been thoroughly characterized (S. T. Crooke, 1992, 1993; see S. T. Crooke and Lebleu, 1993, for reviews). 5"C less per nucleotide than that for a corresponding phosphodiester oligodeoxynucleotide.
1996), thus in a similar range with aspirin or penicillin (Joos and Hall, 1969). Furthermore, in this study, no competition between phosphorothioate oligonucleotides and several drugs that bind to bovine serum albumin was observed. In this study, binding and competition were determined in an assay in which electrospray mass spectrometry was used. In contrast, in a study in which an equilibrium dissociation constant was derived from an assay using albumin loaded on a CH-Sephadex column, M for bovine serum albumin and from the K, ranged from 1 to 5 X M for human serum albumin.