title: Site-Specific Radiofluorination of Biomolecules with 8-[(18)F]-Fluorooctanoic Acid Catalyzed by Lipoic Acid Ligase.
abstract: New methodologies for site-specifically radiolabeling proteins with (18)F are required to generate high quality radiotracers for preclinical and clinical applications with positron emission tomography. Herein, we report an approach by which we use lipoic acid ligase (LplA) to conjugate [(18)F]-fluorooctanoic acid to an antibody fragment bearing the peptide substrate of LplA. The mild conditions of the reaction preserve antibody immunoreactivity, and the efficiency of LplA allows for >90% yield even with very small amounts of peptidic precursor (1-10 nmol). These features are advantageous compared to the current gold standard in the field. Moreover, the methodology introduces a new application for an important tool in chemical biology.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco , Suite 350, 185 Berry Street, San Francisco, California 94107, United States.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Drake
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco , Genentech Hall, S-514, 600 16th Street, San Francisco, California 94158, United States.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sevillano
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco , Suite 350, 185 Berry Street, San Francisco, California 94107, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Truillet
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco , Genentech Hall, S-514, 600 16th Street, San Francisco, California 94158, United States.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Craik
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco , Suite 350, 185 Berry Street, San Francisco, California 94107, United States.
authors.forename: Henry F
authors.initials: HF
authors.lastname: VanBrocklin
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco , Suite 350, 185 Berry Street, San Francisco, California 94107, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Evans
mesh_terms: D002210:Caprylates / Q000138:chemical synthesis / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D005462:Fluorine Radioisotopes; D057809:HEK293 Cells; D054879:Halogenation; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D008025:Ligases / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry
chemical_list: D002210:Caprylates; D029968:Escherichia coli Proteins; D005462:Fluorine Radioisotopes; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; C490345:lplA protein, E coli; C108006:8-fluorooctanoic acid; D008025:Ligases