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A Localized Tolerance in the Substrate Specificity of the Fluorinase Enzyme enables “Last‐Step” 18 F Fluorination of a RGD Peptide under Ambient Aqueous Conditions
Author(s) -
Thompson Stephen,
Zhang Qingzhi,
Onega Mayca,
McMahon Stephen,
Fleming Ian,
Ashworth Sharon,
Naismith James H.,
Passchier Jan,
O'Hagan David
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201403345
Subject(s) - substrate (aquarium) , chemistry , aqueous solution , linker , bioconjugation , acetylene , stereochemistry , combinatorial chemistry , organic chemistry , oceanography , computer science , geology , operating system
A strategy for last‐step 18 F 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 18 F labelling. The method uses an aqueous solution (H 2 18 O) of [ 18 F]fluoride generated by the cyclotron and has the capacity to isotopically label peptides of choice for positron emission tomography (PET).