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 Ónega, Stephen McMahon, Ian Fleming, Sharon Ashworth, Jim Naismith, Jan Passchier, David O'Hagan

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)
2 Downloads (Pure)

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 (H218O) 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

Keywords

  • Bioconjugated peptides
  • Enzyme catalysis
  • Fluorinase
  • Fluorine-18
  • Positron emission tomography

Fingerprint

Dive into the research topics of 'A localized tolerance in the substrate specificity of the fluorinase enzyme enables "last-step" 18F fluorination of a RGD peptide under ambient aqueous conditions'. Together they form a unique fingerprint.

Cite this