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 [(18)F] 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 [(18)F] prosthetic group.
Department of Chemistry, University of Liege (ULg), 13 allée du 6 aout, B-4000 Liege (Sart-tilman), Belgium. jflagothier@ulg.ac.be
Jessica
J
Flagothier
Geoffroy
G
Kaisin
Frederic
F
Mercier
David
D
Thonon
Nathalie
N
Teller
Johan
J
Wouters
André
A
Luxen
D000480:Alkynes / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D034741:RNA, Small Interfering / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization
D000480:Alkynes; D005462:Fluorine Radioisotopes; D034741:RNA, Small Interfering