A localized tolerance in the substrate specificity of the fluorinase enzyme enables "last-step" 18F fluorination of a RGD peptide under ambient aqueous conditions

Stephen Thompson, Qingzhi Zhang, Mayca Onega, Stephen McMahon, Ian Fleming, Sharon Ashworth, James H. Naismith, Jan Passchier, David O'Hagan*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

A strategy for last-step 18F 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 18F labelling. The method uses an aqueous solution (H2 18O) of [ 18F]fluoride generated by the cyclotron and has the capacity to isotopically label peptides of choice for positron emission tomography (PET).

Original languageEnglish
Pages (from-to)8913-8918
Number of pages6
JournalAngewandte Chemie International Edition
Volume53
Issue number34
Early online date2 Jul 2014
DOIs
Publication statusPublished - 18 Aug 2014

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Keywords

  • bioconjugated peptides
  • enzyme catalysis
  • fluorinase
  • fluorine-18
  • positron emission tomography

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

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