Author(s)

S. Thompson, Q. Z. Zhang, M. Onega, S. McMahon, I. Fleming, S. Ashworth, J. H. Naismith, J. Passchier, D. O. Hagan

ISBN

1433-7851

Publication year

2014

Periodical

Angewandte Chemie-International Edition

Periodical Number

34

Volume

53

Pages

8913-8918

Author Address

Hagan, DO Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Imanova, London W12 0NN, England Univ Aberdeen, Sch Med & Dent, Aberdeen Biomed Imaging Ctr, Aberdeen AB25 2ZD, Scotland

Full version

A strategy for last-step F-18 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 (CID EA) 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 F-18 labelling. The method uses an aqueous solution ((H2O)-O-18) of [F-18]fluoride generated by the cyclotron and has the capacity to isotopically label peptides of choice for positron emission tomography (PET).