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

40 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

Keywords

bioconjugated peptides
enzyme catalysis
fluorinase
fluorine-18
positron emission tomography

Access to Document

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

@article{f6cc78d00bd0432790bc08dff2fadc08,

title = "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 = "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).",

keywords = "bioconjugated peptides, enzyme catalysis, fluorinase, fluorine-18, positron emission tomography",

author = "Stephen Thompson and Qingzhi Zhang and Mayca Onega and Stephen McMahon and Ian Fleming and Sharon Ashworth and Naismith, {James H.} and Jan Passchier and David O'Hagan",

note = "Funded by ERC EPSRC Scottish Imaging Network (SINAPSE) John and Kathleen Watson Scholarship",

year = "2014",

month = aug,

day = "18",

doi = "10.1002/anie.201403345",

language = "English",

volume = "53",

pages = "8913--8918",

journal = "Angewandte Chemie International Edition",

issn = "1433-7851",

publisher = "WILEY-V C H VERLAG GMBH",

number = "34",

}

TY - JOUR

T1 - A localized tolerance in the substrate specificity of the fluorinase enzyme enables "last-step" 18F fluorination of a RGD peptide under ambient aqueous conditions

AU - Thompson, Stephen

AU - Zhang, Qingzhi

AU - Onega, Mayca

AU - McMahon, Stephen

AU - Fleming, Ian

AU - Ashworth, Sharon

AU - Naismith, James H.

AU - Passchier, Jan

AU - O'Hagan, David

N1 - Funded by ERC EPSRC Scottish Imaging Network (SINAPSE) John and Kathleen Watson Scholarship

PY - 2014/8/18

Y1 - 2014/8/18

N2 - 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).

AB - 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).

KW - bioconjugated peptides

KW - enzyme catalysis

KW - fluorinase

KW - fluorine-18

KW - positron emission tomography

UR - http://www.scopus.com/inward/record.url?scp=84906101904&partnerID=8YFLogxK

U2 - 10.1002/anie.201403345

DO - 10.1002/anie.201403345

M3 - Article

AN - SCOPUS:84906101904

VL - 53

SP - 8913

EP - 8918

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

SN - 1433-7851

IS - 34

ER -

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

Keywords

Access to Document

Other files and links

Fingerprint

Ian Fleming

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Profiles

Ian Fleming

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