What problems can occur, when oxygen been replaced for a sulfur in a phosphorothioated oligo?
This leads to a mixture of isomers at each incorporation site, resulting in 2n-1 isomers for an oligo of length n. Initially, there was much concern that this isomer mix would give unpredictable results. Fortunately, while short isomers are separable by HPLC and have a somewhat different resistance to nucleases, the isomer mix in any standard S-oligo preparation does not appear to affect the biological activity of the oligonucleotides. They may contribute to some of the non-specific binding observed with phophorothioate oligos. The more thioated bonds you have, the larger the number of enantiomers of your oligo you will have. This is part of the reason we suggest capping the ends of your oligo rather than thioating the entire backbone.
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12/15/2008