title: A localized tolerance in the substrate specificity of the fluorinase enzyme enables "last-step" 18F fluorination of a RGD peptide under ambient aqueous conditions.
abstract: 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).
authors.affiliation: School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST (UK).
authors.forename: Stephen
authors.initials: S
authors.lastname: Thompson
authors.forename: Qingzhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mayca
authors.initials: M
authors.lastname: Onega
authors.forename: Stephen
authors.initials: S
authors.lastname: McMahon
authors.forename: Ian
authors.initials: I
authors.lastname: Fleming
authors.forename: Sharon
authors.initials: S
authors.lastname: Ashworth
authors.forename: James H
authors.initials: JH
authors.lastname: Naismith
authors.forename: Jan
authors.initials: J
authors.lastname: Passchier
authors.forename: David
authors.initials: D
authors.lastname: O'Hagan
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005461:Fluorine / Q000737:chemistry*; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D010088:Oxidoreductases / Q000737:chemistry*; D011487:Protein Conformation; D011854:Radiochemistry; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D009842:Oligopeptides; D014867:Water; D005461:Fluorine; C047981:arginyl-glycyl-aspartic acid; D010088:Oxidoreductases; C495766:fluorinase
keywords: bioconjugated peptides; enzyme catalysis; fluorinase; fluorine-18; positron emission tomography