A localized tolerance in the substrate specificity of the fluorinase enzyme enables "last-step" 18F fluorination of a RGD peptide under ambient aqueous conditions
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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).
Thompson , S , Zhang , Q , Ónega , M , McMahon , S , Fleming , I , Ashworth , S , Naismith , J , Passchier , J & O'Hagan , D 2014 , ' 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 ' , Angewandte Chemie International Edition , vol. 53 , no. 34 , pp. 8913-8918 . https://doi.org/10.1002/anie.201403345
Angewandte Chemie International Edition
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the accepted version of the following article: Thompson, S., Zhang, Q., Onega, M., McMahon, S., Fleming, I., Ashworth, S., Naismith, J. H., Passchier, J. and O'Hagan, D. (2014), A Localized Tolerance in the Substrate Specificity of the Fluorinase Enzyme enables “Last-Step” 18F Fluorination of a RGD Peptide under Ambient Aqueous Conditions. Angew. Chem. Int. Ed., 53: 8913–8918, which has been published in final form at http://dx.doi.org/10.1002/anie.201403345
DescriptionThe authors thank the ERC, EPSRC and the Scottish Imaging Network (SINAPSE) for grants, and the John and Kathleen Watson Scholarship (S.T.) for financial support.
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