Poster (Scientific congresses and symposiums)
Universal solid support synthesis of modified oligonucleotides labeled by click chemistry for PET studies
Flagothier, Jessica; Mercier, Frederic; Kaisin, Geoffroy et al.
20094th European Molecular Imaging Meeting of the ESMI
 

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Keywords :
oligonucleotide; Click chemistry; fluorine 18
Abstract :
[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.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Chemistry
Author, co-author :
Flagothier, Jessica ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse
Mercier, Frederic
Kaisin, Geoffroy ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Thonon, David ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Lemaire, Christian ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Luxen, André ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse
Language :
English
Title :
Universal solid support synthesis of modified oligonucleotides labeled by click chemistry for PET studies
Publication date :
29 May 2009
Event name :
4th European Molecular Imaging Meeting of the ESMI
Event organizer :
European Society for Molecular Imaging
Event place :
Barcelona, Spain
Event date :
27/05 au 30/05
Audience :
International
Name of the research project :
OligoPET
Funders :
Région wallonne [BE]
ULg - Université de Liège [BE]
Available on ORBi :
since 30 July 2011

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