|Reference : Universal solid support synthesis of modified oligonucleotides labeled by click chemi...|
|Scientific congresses and symposiums : Poster|
|Physical, chemical, mathematical & earth Sciences : Chemistry|
|Universal solid support synthesis of modified oligonucleotides labeled by click chemistry for PET studies|
|Flagothier, Jessica [Université de Liège - ULg > Département de chimie (sciences) > Chimie organique de synthèse >]|
|Mercier, Frederic [ > > ]|
|Kaisin, Geoffroy [Université de Liège - ULg > > Centre de recherches du cyclotron >]|
|Thonon, David [Université de Liège - ULg > > Centre de recherches du cyclotron >]|
|Lemaire, Christian [Université de Liège - ULg > > Centre de recherches du cyclotron >]|
|Luxen, André [Université de Liège - ULg > Département de chimie (sciences) > Chimie organique de synthèse >]|
|4th European Molecular Imaging Meeting of the ESMI|
|27/05 au 30/05|
|European Society for Molecular Imaging|
|[en] oligonucleotide ; Click chemistry ; fluorine 18|
|[en] Introduction: Positron emission tomography (PET) is a high-resolution, sensitive, molecular and functional imaging technique that permits repeated, non invasive assessment and quantification of specific biological and pharmacological processes in humans. In regard to its physical and nuclear characteristics, fluorine-18 appears often as the radionuclide of choice for the preparation of short-lived positron-emitter radiotracers. F-18 labelling reaction of biomolecules such as peptides, oligosaccharides, and oligonucleotides (ONs) requires very mild reaction conditions. The method of choice for a highly efficient fluorine-18-labelling of ONs is today the conjugation of a prosthetic group, carrying the radioisotope, with a reactive function of the ONs.
Methods: For the ligation reaction of the prosthetic group with the ONs, we selected click reaction and more particularly the CuI catalyzed formation of 1,2,3-triazole using Huisgen 1,3-dipolar cycloaddition of terminal alkynes with azides. This reaction is highly regioselective leading to 1,4-disubstituted 1,2,3-triazoles and can be performed in different solvents with very high yield[5-7].
Conjugations with ONs are usually performed at 3’-ends using a well chosen linker in order to limit degradation by exonucleases. Here we report the synthesis of an alkyne-bearing linker which can be attached at 3’-ends to any sequence of ONs.
Results: The linker was prepared in two steps by reaction of commercially available (R)-(+)--hydroxy--butyrolactone with propargylamine followed by protection of the primary hydroxyl with the 4,4’-dimethoxytrityl group. The second step is the reaction with succinic anhydride to obtain a carboxylic function which can be attached to the Amino-SynBase CPG. The resin load was 80 µmol/g.
Conclusions: We have prepared a new universal linker which allows introducing an alkyne function at the 3’-end of ONs. This alkyne modified ONs can then react under click conditions with an azide function of a prosthetic group carrying the fluorine radioisotope. As prosthetic group, we selected the 1-azido-4-(3-[18F]fluoropropoxy)benzene which is fully automated produce in our lab. The further results of radiosynthesis of this prosthetic group and the results of click reactions will be presented.
Acknowledgement: The authors wish to thank Teller N. from Eurogentec (Seraing, Belgium) for oligonucleotide synthesis. The authors wish to acknowledge the financial support from the Oligopet Projet of the Walloon Region.
|Centre de Recherches du Cyclotron - CRC|
|Région Wallonne, ULg|
|Researchers ; Professionals|
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