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

doi:10.1002/anie.201403345

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 journal › Article › peer-review

41 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 language	English
Pages (from-to)	8913-8918
Number of pages	6
Journal	Angewandte Chemie International Edition
Volume	53
Issue number	34
Early online date	2 Jul 2014
DOIs	https://doi.org/10.1002/anie.201403345
Publication status	Published - 18 Aug 2014

Bibliographical note

Funded by
ERC
EPSRC
Scottish Imaging Network (SINAPSE)
John and Kathleen Watson Scholarship

Keywords

bioconjugated peptides
enzyme catalysis
fluorinase
fluorine-18
positron emission tomography

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10.1002/anie.201403345

Cite this

Thompson, S., Zhang, Q., Onega, M., McMahon, S., Fleming, I., Ashworth, S., Naismith, J. H., Passchier, J., & 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. Angewandte Chemie International Edition, 53(34), 8913-8918. https://doi.org/10.1002/anie.201403345

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

Research output: Contribution to journal › Article › peer-review

Thompson, S, Zhang, Q, Onega, M, McMahon, S, Fleming, I, Ashworth, S, Naismith, JH, Passchier, J & 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', Angewandte Chemie International Edition, vol. 53, no. 34, pp. 8913-8918. https://doi.org/10.1002/anie.201403345

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

Abstract

Bibliographical note

Keywords

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Ian Fleming

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

Abstract

Bibliographical note

Keywords

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Ian Fleming

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