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

27 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

Fingerprint

Acetylene
Fluorination
Peptides
Enzymes
Positron emission tomography
Cyclotrons
Substrates
Fluorides
Adenosine
Labeling
Polyethylene glycols
Labels
fluorinase
arginyl-glycyl-aspartic acid

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

Cite this

A localized tolerance in the substrate specificity of the fluorinase enzyme enables "last-step" 18F fluorination of a RGD peptide under ambient aqueous conditions. / Thompson, Stephen; Zhang, Qingzhi; Onega, Mayca; McMahon, Stephen; Fleming, Ian; Ashworth, Sharon; Naismith, James H.; Passchier, Jan; O'Hagan, David.

In: Angewandte Chemie International Edition, Vol. 53, No. 34, 18.08.2014, p. 8913-8918.

Research output: Contribution to journalArticle

Thompson, Stephen ; Zhang, Qingzhi ; Onega, Mayca ; McMahon, Stephen ; Fleming, Ian ; Ashworth, Sharon ; Naismith, James H. ; Passchier, Jan ; O'Hagan, David. / A localized tolerance in the substrate specificity of the fluorinase enzyme enables "last-step" 18F fluorination of a RGD peptide under ambient aqueous conditions. In: Angewandte Chemie International Edition. 2014 ; Vol. 53, No. 34. pp. 8913-8918.
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