Fig. 1

Schematic structure of two nucleotides linked together with a phosphorothioate bridge. Starting from the 5′-end: DNA-based adenosine and LNA-based uridine derivative. The standard numbering convention is shown on the purine ring in blue numbers from 1 through 9 on the aromatic base. Thiol or amine functionalized linker (Fig. 2) is connected to phosphorothioate at 3′-end. The circled numbers represent the labeling approaches: (1) hydrogen-tritium exchange by the use of tritiated water or tritium gas and ruthenium nanoparticles, (2) palladium catalyzed bromo-tritium exchange, (3) oxidation of 5′-alcohol and reduction with sodium borotritide, and (4) hydrogen-tritium exchange by the use of tritium gas and ruthenium nanoparticles