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

摘要

A strategy for last-step ~(18)F fluorination of bioconju-gatcd 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-ethynyl-adenosine (CIDEA) to 5'-fluorodeoxy-2-ethynyladenosine (FDEA). Extending a polyethylene glycol linker from the terminus of the acetylene allows the presentation of bioconju-gation cargo to the enzyme for ~(18)F labelling. The method uses an aqueous solution (H_2~(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).