title: 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.
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 ([18F]F-SA) as a novel aromatic sulfonamide-based click chemistry building block. [18F]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 [18F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [18F]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 [18F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter 18F.
authors.affiliation: Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
authors.forename: Theres
authors.initials: T
authors.lastname: Ramenda
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
mesh_terms: D057930:Click Chemistry / Q000379:methods; D003300:Copper / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling; D010748:Phosphopeptides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry*; D000096926:Benzenesulfonamides
chemical_list: D003300:Copper; D005462:Fluorine Radioisotopes; D010748:Phosphopeptides; D012313:RNA; D019275:Radiopharmaceuticals; D012709:Serum Albumin; D013449:Sulfonamides; D000096926:Benzenesulfonamides