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

Angewandte Chemie (International ed. in English)

PubMedID: 24989327

Thompson S, Zhang Q, Onega M, McMahon S, Fleming I, Ashworth S, Naismith JH, Passchier J, O'Hagan D. A Localized Tolerance in the Substrate Specificity of the Fluorinase Enzyme enables "Last-Step" (18) F Fluorination of a RGD Peptide under Ambient Aqueous Conditions. Angew Chem Int Ed Engl. 2014;.
A strategy for last-step (18) F 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 (18) F labelling. The method uses an aqueous solution (H2 (18) O) of [(18) F]fluoride generated by the cyclotron and has the capacity to isotopically label peptides of choice for positron emission tomography (PET).