Bioconjugate Chemistry 2011-01-19

General method for labeling siRNA by click chemistry with fluorine-18 for the purpose of PET imaging.

Frédéric Mercier, Jérôme Paris, Geoffroy Kaisin, David Thonon, Jessica Flagothier, Nathalie Teller, Christian Lemaire, André Luxen

Index: Bioconjug. Chem. 22 , 108-114, (2011)

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Abstract

The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click-type reaction, was used to label a double-stranded oligonucleotide (siRNA) with fluorine-18. An alkyne solid support CPG for the preparation of monostranded oligonucleotides functionalized with alkyne has been developed. Two complementary azide labeling agents (1-(azidomethyl)-4-[(18)F]fluorobenzene) and 1-azido-4-(3-[(18)F]fluoropropoxy)benzene have been produced with 41% and 35% radiochemical yields (decay-corrected), respectively. After annealing with the complementary strand, the siRNA was directly labeled by click chemistry with [(18)F]fluoroazide to produce the [(18)F]-radiolabeled siRNA with excellent radiochemical yield and purity.


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