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Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging
Kaisin, Geoffroy; Flagothier, Jessica; Mercier, Frédéric et al.
2009Learning Organic Synthesis Tremendously (LOST II)
 

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Abstract :
[en] Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their pharmacokinetics and biodistributions are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to image and quantify such biological processes. The challenge for the radiochemist is to introduce this short half-life isotope (t1/2(18F)=109.7 min) onto oligonucleotides or, more generally, biomolecules. The most common technique requires the coupling of a prosthetic group bearing the radiotracer with the biomolecule. Current methods for labeling ONs with fluorine-18 have sub-optimal yields and require a long synthesis time.{Vries2003} Click chemistry, e.g. 1,3-dipolar Huisgen cycloaddition of azides to alkynes, could be an efficient way to increase yields and reduce synthesis time (see Figure 1). This family of reactions are well suited to the radiolabelling of ONs as they are tolerant to a wide range of solvent and require mild reaction conditions and simple purifications.{Glaser2007} The major strength of this approach is its versatility: it can be easily transposed to any other kind of biomolecules (e.g. peptides, lipids) as long as they can bear an azido or alkyne moiety. Conjugations with ONs are usually performed at 3’-ends using a well-chosen linker in order to limit degradation by exonucleases and to avoid alteration of hybridization properties and siRNA gene silencing efficiency.{Kurreck2009} This also allows the development of universal solid support because synthesis occurs from the 3’ to 5’-end. The linker must fulfil a number of requirements:{Gait2001} - Bearing one alkyne, one primary and one secondary alcohol moiety; - Having a well-defined and known stereochemistry. According to these terms, we propose three different potential linkers (see Figure 2) that can be incorporated into the solid-phase synthesis of ONs. Starting materials are commercially available as pure enantiomers at an affordable price. Here we report the synthesis and characterisation of an alkyne-bearing linker and the synthesis and radiosynthesis of the complementary azido-bearing prosthetic groups (1-(azidomethyl)-4-[18F]-fluorobenzene).
Disciplines :
Chemistry
Author, co-author :
Kaisin, Geoffroy ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Flagothier, Jessica ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse
Mercier, Frédéric
Thonon, David ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Paris, Jérôme ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Kech, Cécile
Lemaire, Christian ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Plenevaux, Alain  ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Luxen, André ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron
Language :
English
Title :
Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging
Publication date :
18 March 2009
Event name :
Learning Organic Synthesis Tremendously (LOST II)
Event organizer :
FUNDP
Event place :
Namur, Belgium
Event date :
du 18 au 20 mars 2009
Audience :
International
Available on ORBi :
since 02 February 2011

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