A novel sulfonated prosthetic group for [18F]-radiolabelling and imparting water solubility of biomolecules and cyanine fluorophores.

Synthesis and some applications of a novel [(18)F]-fluorinated prosthetic group based on the promising sultone radiochemistry and suitable for the labelling of amine-containing (bio)chemical compounds are described. The combined sequential use of two easy and efficient conjugation reactions namely the fluoride ring-opening of a 1,3-propanesultone moiety and the aminolysis of an N-hydroxysuccinimidyl ester is the key component of this original radiolabelling strategy. The mild reaction conditions and the release of a free sulfonic acid moiety as a result of the [(18)F]-induced sultone ring-opening reaction, both make this [(18)F]-conjugation method suitable for the radiofluorination of fragile and hydrophobic biomolecules and fluorophores, particularly by making the separation of the targeted [(18)F]-tagged sulfonated compound from its starting precursor easier and thus faster. The ability of this unusual prosthetic group to readily introduce the radioisotope within complex (bio)molecular architectures has been demonstrated by (1) the preparation of the first [(18)F]-labelled cyanine 5.5 (Cy 5.5) dye, a suitable precursor for the construction of hybrid positron emission tomography/near-infrared fluorescence (PET/NIRF) imaging probes and (2) the radiolabelling of a biologically relevant peptide bearing a single lysine residue.

Synthesis and reactivity of a bis-sultone cross-linker for peptide conjugation and [18F]-radiolabelling via unusual "double click" approach.

A novel homobifunctional cross-linker based on a bis-sultone benzenic scaffold was synthesised. The potential utility of this bioconjugation reagent was demonstrated through the preparation of an original prosthetic group suitable for the [(18)F]-labelling of peptides. The labelling strategy is based on the nucleophilic fluorination via the ring-opening of a first sultone moiety followed by the nucleophilic ring-opening of the second remanent sultone by a reactive amine of the biopolymer. Beyond the one-step radiolabelling of the peptide, the second main advantage of this strategy is the release of free sulfonic acid moieties making the separation of the targeted [(18)F]-tagged sulfonated compound from its non-sulfonated precursor easier and thus faster. This first report of the successful use of a bis-sultone moiety as a versatile bioconjugatable group was demonstrated through a comprehensive reactivity study involving various nucleophiles, especially those commonly found in biopolymers. An illustrative example, highlighting the potential of this unusual and promising "double click" conjugation approach, was devoted to the radiolabelling of a biological relevant peptide.