  Click chemistry : radiolabelling of oligonucleotides with fluorine- 18 for PETKaisin, Geoffroy  ; Flagothier, Jessica ; Mercier, Frédéric et alPoster (2010, June) Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their pharmacokinetics and biodistributions are widely unknown. Positron Emission Tomography (PET ... [more ▼] 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.1 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. 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. This also allows the development of universal solid supports used for the solidphase synthesis of ONs. Here we report the synthesis of three alkyne-bearing linkers , the synthesis and radiosynthesis of the complementary azido-bearing prosthetic groups (1-(azidomethyl)-4-[18F]- fluorobenzene) and coupling with functionalized ONs. [less ▲] Detailed reference viewed: 105 (32 ULg) PEPTIDE CLICK LABELLING WITH 1-(AZIDOMETHYL)-4-[18F]-FLUOROBENZENE AND REFERENCE COMPOUNDS SYNTHESIS ON SOLID SUPPORTThonon, David ; Paris, Jérôme ; et alin Journal of Labelled Compounds and Radiopharmaceuticals (2009, July) Detailed reference viewed: 21 (3 ULg)New Strategy for the Preparation of Clickable Peptides and Labeling with 1-(Azidomethyl)-4-[18F]-fluorobenzene for PETThonon, David ; Paris, Jérôme ; et alin Bioconjugate Chemistry (2009), 20(4), 817-823 The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click type reaction was used to label a peptide with fluorine-18. A novel solid phase synthesis approach for the preparation of clickable peptides ... [more ▼] The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click type reaction was used to label a peptide with fluorine-18. A novel solid phase synthesis approach for the preparation of clickable peptides has been developed and has also permitted the straightforward preparation of reference compounds. A complementary azide labeling agent (1-(azidomethyl)-4-[18F]-fluorobenzene) has been produced in a four step procedure in 75 min with a 34% radiochemical yield (decay corrected). Conjugation of [18F]fluoroazide with a model alkyne-neuropeptide produced the desired 18F-radiolabeled peptide in less than 15 min with a yield of 90% and excellent radiochemical purity [less ▲] Detailed reference viewed: 19 (5 ULg)Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imagingKaisin, Geoffroy ; Flagothier, Jessica ; et alPoster (2009, March 18) Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their ... [more ▼] 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). [less ▲] Detailed reference viewed: 24 (10 ULg)18F LABELING OF BIOMOLECULES USING CLICK CHEMISTRY FOR PET APPLICATIONS : SYNTHETIC DEVELOPMENTSThonon, David ; Flagothier, Jessica ; Paris, Jérôme et alin Drugs of the Future (2008, August), 33(A), 235 Detailed reference viewed: 60 (15 ULg)Click chemistry for 18F labelling of bioactive compoundsParis, Jérôme ; Thonon, David ; et alPoster (2008, July 03) Detailed reference viewed: 6 (0 ULg)Click Chemistry Based Labeling of Biomolecules with 18F: a New Method to Produce PET Molecular Tracers.Thonon, David ; ; Lemaire, Christian et alPoster (2008) Detailed reference viewed: 13 (1 ULg) |
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