No abstract

Take it eaSi! Nucleosides, dinucleotides, and one oligonucleotide, all modified by click chemistry, have for the first time been directly and very efficiently labeled with (18)F by using a silicon-based, one-step approach that opens the way for the development of a new class of positron emission tomography (PET) tracers (see graphic).

Positron Emission Tomography has become a powerful scientific and clinical tool probing biochemical processes in the human body. Their clinical applications have proven to be vital in the evaluation and diagnosis of diseases. This is due, in large part, to advances in instrumentation and synthetic chemistry. Carbon-11 is a valuable radionuclide in PET as it virtually permits the synthesis of radiolabelled versions of any compound of interest. The syntheses with carbon-11 present several features: limited number of labelled precursors, sub-micromolar amounts of the starting materials, and a need for the introduction of the radioisotope as late as possible in the synthesis. All of these reasons have restricted complex radiosyntheses. The short half-life of carbon-11 (20.4 min) requires the rapid preparation and purification of carbon-11 labelled molecules. Those have to be carried out immediately before use from cyclotron produced precursors ([11C]CO2, [11C]CO, [11C]CH4) or reagents rapidly prepared from them ([11C]CH3I, [11C]COCl2, [11C]HCN). As a consequence carbon-11 has been underused compared to fluorine-18. However, because of the increasing molecular complexity and diversity of biologically active compounds, there is a need for new methodologies giving access in short time and high yield to radioactive (11)C-probes. The aim of this review is to emphasize the methodologies used in this field and to give a comprehensive overview of the numerous advances, which occurred over the past decade. In addition, for each labelling technique or reaction reported, a special attention has been brought to classify the applications in function of the targeted medical domain.

This communication reports the simplified formation of methyl azide and its use in the Huisgen cycloaddition for the rapid, efficient, and selective labeling of modified nucleosides and oligonucleotides. The transposition to radioactive chemistry is presented, and this furnishes practical access to [11C]methylated tracers for positron emission tomography imaging.

Abstract:The methyl transfer reaction from activated monomethyltin, via a modified Stille coupling reaction, was studied under "ligandless" conditions on fully deprotected 5'-modified nucleosides and one dinucleotide. The reaction was optimized to proceed in a few minutes and quantitative yield, even under dilute conditions, thus affording a rapid and efficient new method for oligonucleotide labelling with carbon-11.

UDP-glucuronosyltransferase 1A1 (UGT1A1) is av ital metabolic enzyme responsible for the clearance of endogenous substances and drugs.H itherto,t he development of fluorescent probes for UGTs was severely restricted due to the poor isoform selectivity and on-off or blue-shifted fluorescence response.Herein, we established anovel "molecular-splicing" strategy to construct ah ighly selective nearinfrared (NIR) fluorescent probe, HHC,f or UGT1A1, which exhibited aN IR signal at 720 nm after UGT1A1 metabolism. HHC was then successfully used for the real-time imaging of endogenous UGT1A1 in living cells and animals and to monitor the bile excretion function. In summary,a ni soformspecific NIR fluorescent probe has been developed for monitoring UGT1A1 activity in living systems,h igh-throughput screening of novel UGT1A1 inhibitors and visual evaluation of bile excretion function.