4-[18F]Fluoro-N-methyl-N-(prop-2-ynyl)benzenesulfonamide: A novel prosthetic group for click chemistry with peptides and proteins


4-[18F]Fluoro-N-methyl-N-(prop-2-ynyl)benzenesulfonamide: A novel prosthetic group for click chemistry with peptides and proteins

Ramenda, T.; Knieß, T.; Steinbach, J.; Wüst, F.

Ziel/Aim:

The radiolabeling of peptides or proteins with the short-lived positron emitter 18F requires rapid and mild reaction conditions to maintain the structural and functional integrity of these bioactive compounds. Over the last two years several approaches have been published focused on the application of copper(I)-mediated 1,3-dipolar [3+2]cycloaddition of azides and alkynes for labeling peptides with 18F.1-4 The peptides were functionalized with an azide- or alkyne group to be reacted with an appropriately 18F-labeled azide or alkyne, respectively. In this work we report on the radiosynthesis and application of a novel 18F-labeled prosthetic group based upon a sulfonamide backbone suitable for click chemistry applications using azide-functionalized phosphopeptide and human serum albumin (HSA).

Methodik/Methods:

Two labeling precursors containing different leaving groups (nitro- and trimethylammoniumtriflate) and the reference substance were prepared by the reaction of N-methylpropargylamine with the corresponding sulfonic acid chlorides. Radiofluorination was performed in a single step. Different purification procedures have been developed including solid phase extraction and semi-preparative HPLC. The peptide and the protein were modified with an azide linker. Cycloaddition reactions were carried out in the presence of copper(I) salts in combination with different copper-chelating ligand systems.

Ergebnisse/Results:

The radiolabeled sulfonamide can be obtained in radiochemical yields of 23 % (decay corrected) in high radiochemical purity of >99 % after HPLC purification within 89 min. First promising results in labeling a phosphopeptide and a protein (HSA) could be achieved.

Schlussfolgerungen/Conclusions:

The novel prosthetic group for peptide and protein labeling with 18F via click chemistry can be prepared in reasonable radiochemical yields and high radiochemical purity. Moreover, for the first time click chemistry was successfully applied to the 18F labeling of a a phosphopeptide and a protein.

Figuren/Figures:


4-[18F]Fluoro-N-methyl-N-(prop-2-ynyl)benzenesulfonamide

Referenzen/Refrences:

1 Marik, J.; Sutcliffe, J.L. Tetrahedron Lett., 2006, 47, 6681.
2 Ramenda, T.; Bergmann, R.; Wuest, F. Lett. Drug Des. Discovery, 2007, 4, 279.
3 Glaser, M.; Arstad, E. Bioconjugate Chem., 2007, 18, 989.
4 Li, Z.-B.; Wu, Z.; Chen, K.; Chin, F.T.; Chen, X. Bioconjugate Chem., 2007, 18, 1987.

  • Lecture (others)
    16. Arbeitstagung der AG Radiochemie/Radiopharmazie, 25.-27.09.2008, Münster, Deutschland

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Publ.-Id: 11620