Reference : Universal solid support synthesis of modified oligonucleotides labeled by click chemi...
Scientific congresses and symposiums : Poster
Physical, chemical, mathematical & earth Sciences : Chemistry
http://hdl.handle.net/2268/96349
Universal solid support synthesis of modified oligonucleotides labeled by click chemistry for PET studies
English
Flagothier, Jessica mailto [Université de Liège - ULg > Département de chimie (sciences) > Chimie organique de synthèse >]
Mercier, Frederic [ > > ]
Kaisin, Geoffroy mailto [Université de Liège - ULg > > Centre de recherches du cyclotron >]
Thonon, David mailto [Université de Liège - ULg > > Centre de recherches du cyclotron >]
Lemaire, Christian mailto [Université de Liège - ULg > > Centre de recherches du cyclotron >]
Luxen, André mailto [Université de Liège - ULg > Département de chimie (sciences) > Chimie organique de synthèse >]
29-May-2009
Yes
No
International
4th European Molecular Imaging Meeting of the ESMI
27/05 au 30/05
European Society for Molecular Imaging
Barcelona
Spain
[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[1]. 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[2]. F-18 labelling reaction of biomolecules such as peptides[3], oligosaccharides, and oligonucleotides[4] (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[8]. 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[9]. 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[10]. 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
OligoPET
Researchers ; Professionals
http://hdl.handle.net/2268/96349

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