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4-[18F]Fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([18F]F-SA): a versatile building block for labeling of peptides, proteins and oligonucleotides with fluorine-18 via Cu(I)-mediated click chemistry

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Abstract

Cu(I)-mediated [3+2]cycloaddition between azides and alkynes has evolved into a valuable bioconjugation tool in radiopharmaceutical chemistry. We have developed a simple, convenient and reliable radiosynthesis of 4-[18F]fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([ 18 F]F-SA) as a novel aromatic sulfonamide-based click chemistry building block. [ 18 F]F-SA could be prepared in a remotely controlled synthesis unit in 32 ± 5 % decay-corrected radiochemical yield in a total synthesis time of 80 min. The determined lipophilicity of [ 18 F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [ 18 F]F-SA as click chemistry building block was demonstrated by the labeling of a model peptide (phosphopeptide), protein (HSA), and oligonucleotide (L-RNA). The obtained radiochemical yields were 77 % (phosphopeptide), 55–60 % (HSA), and 25 % (L-RNA), respectively. Despite the recent emergence of a multitude of highly innovative novel bioconjugation methods for 18F labeling of biopolymers, Cu(I)-mediated click chemistry with [ 18 F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter 18F.

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Acknowledgments

The authors are grateful to Mareike Barth, Inge Közle, Stephan Preusche and Tilow Krauss for their excellent technical assistance.

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The authors declare that they have no conflict of interest.

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Correspondence to Frank Wuest.

Additional information

Preliminary results on the synthesis and use of the click chemistry building block [ 18 F]F-SA have already been published (Ramenda et al. 2009).

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Ramenda, T., Steinbach, J. & Wuest, F. 4-[18F]Fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([18F]F-SA): a versatile building block for labeling of peptides, proteins and oligonucleotides with fluorine-18 via Cu(I)-mediated click chemistry. Amino Acids 44, 1167–1180 (2013). https://doi.org/10.1007/s00726-012-1450-4

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