Synthesis of two new alkyne-bearing linkers used for the preparation of siRNA for labeling by click chemistry with fluorine-18

Oligonucleotides (ONs) and more particularly siRNAs are promising drugs but their pharmacokinetics and biodistribution are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to quantify these biological processes. Click chemistry (Huisgen cycloaddition) is the current method for labeling siRNA. In order to study the influence of a linker bearing by [18F] labeled ONs, on the in vivo pharmacokinetic and metabolism, we have developed two modified ONs by two new linkers. Here we report the synthesis of two alkyne-bearing linkers, the incorporation onto a ONs and the conjugation by click chemistry with a [18F] prosthetic group.

► Synthesis of two new alkyne linkers.
► Functionalization at the 3′-end siRNA by alkyne linker derived of proline.
► Click chemistry between alkyne modified siRNA and [18F] prosthetic group.