A Versatile and Convenient Synthesis of 34S‐Labeled Phosphorothioate Oligonucleotides |
| |
| Authors: | Rouven Stulz Dr Johan Meuller D?enita Ba?darevi? Dr Charlotte Wennberg?Huldt Prof Roger Strömberg Dr Shalini Andersson Dr Anders Dahlén |
| |
| Affiliation: | 1. Cardiovascular, Renal and Metabolism IMED Biotech Unit, AstraZeneca, M?lndal, Sweden;2. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden;3. Discovery Sciences IMED Biotech Unit, AstraZeneca, M?lndal, Sweden |
| |
| Abstract: | A synthetic protocol for 34S‐labeled phosphorothioate oligonucleotides (PS ONs) was developed to facilitate MS‐based assay analysis. This was enabled by a highly efficient, two‐step, one‐pot synthesis of 34S‐labeled phenylacetyl disulfide (34S‐PADS), starting from 34S‐enriched elemental sulfur (34S8). 34S‐PADS was subsequently used for stable isotope labeling (SIL) of oligonucleotides containing a phosphorothioate backbone. The 34S‐SIL PS ONs are shown to retain the same melting temperature, antisense activity, and secondary structure as those of the corresponding unlabeled 32S PS ONs. |
| |
| Keywords: | antisense agents isotopic labeling oligonucleotides sulfur synthesis design |
|
|
