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

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-[F]fluoro- N-methyl- N-(propyl-2-yn-1-yl)benzenesulfonamide ( [ F]F-SA) as a novel aromatic sulfonamide-based click chemistry building block. [ 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 [ F]F-SA (log P = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [ 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 F labeling of biopolymers, Cu(I)-mediated click chemistry with [ F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter F. [ABSTRACT FROM AUTHOR]