A Localized Tolerance in the Substrate Specificity of the Fluorinase Enzyme enables “Last-Step” 18F Fluorination of a RGD Peptide under Ambient Aqueous Conditions


  • We thank the ERC, EPSRC and the Scottish Imaging Network (SINAPSE) for grants, and the John and Kathleen Watson Scholarship (S.T.) for financial support.


A strategy for last-step 18F fluorination of bioconjugated peptides is reported that exploits an “Achilles heel” in the substrate specificity of the fluorinase enzyme. An acetylene functionality at the C-2 position of the adenosine substrate projects from the active site into the solvent. The fluorinase catalyzes a transhalogenation of 5′-chlorodeoxy-2-ethynyladenosine (ClDEA) to 5′-fluorodeoxy-2-ethynyladenosine (FDEA). Extending a polyethylene glycol linker from the terminus of the acetylene allows the presentation of bioconjugation cargo to the enzyme for 18F labelling. The method uses an aqueous solution (H218O) of [18F]fluoride generated by the cyclotron and has the capacity to isotopically label peptides of choice for positron emission tomography (PET).