Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal 
                        19
                        F MRI Agents

Steven E. Kirberger; Sofia D. Maltseva; Joseph C. Manulik; Samuel A. Einstein; Bradley P. Weegman; Michael Garwood; William C.K. Pomerantz

doi:10.1002/anie.201700426

Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal ¹⁹ F MRI Agents

Steven E. Kirberger, Sofia D. Maltseva, Joseph C. Manulik, Samuel A. Einstein, Bradley P. Weegman, Michael Garwood, William C.K. Pomerantz

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

39 Scopus citations

Abstract

¹⁹F MRI is valuable for in vivo imaging due to the only trace amounts of fluorine in biological systems. Because of the low sensitivity of MRI however, designing new fluorochemicals remains a significant challenge for achieving sufficient ¹⁹F signal. Here, we describe a new class of high-signal, water-soluble fluorochemicals as ¹⁹F MRI imaging agents. A polyamide backbone is used for tuning the proteolytic stability to avoid retention within the body, which is a limitation of current state-of-the-art perfluorochemicals. We show that unstructured peptides containing alternating N-ϵ-trifluoroacetyllysine and lysine provide a degenerate ¹⁹F NMR signal. ¹⁹F MRI phantom images provide sufficient contrast at micromolar concentrations, showing promise for eventual clinical applications. Finally, the degenerate high signal characteristics were retained when conjugated to a large protein, indicating potential for in vivo targeting applications, including molecular imaging and cell tracking.

Original language	English (US)
Pages (from-to)	6440-6444
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	56
Issue number	23
DOIs	https://doi.org/10.1002/anie.201700426
State	Published - Jun 1 2017

Bibliographical note

Funding Information:
This study has been funded via the University of Minnesota McKnight Land Grant Professorship, Research Corporation Cottrell Scholar Award, Heisig-Gleysteen Fellowship, and University of Minnesota Undergraduate Research Scholarship (URS). The MRI work was supported in part by the Minnesota Lions Diabetes Foundation, the Schott Family Foundation, the Carol Olson Memorial Diabetes Research Fund, and the NIH [grants P41 EB015894 and S10 RR025031].

Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

F NMR spectroscopy
fluorination
magnetic resonance imaging
molecular imaging
peptides

Publisher link

10.1002/anie.201700426

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493043

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Cite this

Kirberger, S. E., Maltseva, S. D., Manulik, J. C., Einstein, S. A., Weegman, B. P., Garwood, M., & Pomerantz, W. C. K. (2017). Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal ¹⁹ F MRI Agents. Angewandte Chemie - International Edition, 56(23), 6440-6444. https://doi.org/10.1002/anie.201700426

Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal ¹⁹ F MRI Agents. / Kirberger, Steven E.; Maltseva, Sofia D.; Manulik, Joseph C. et al.
In: Angewandte Chemie - International Edition, Vol. 56, No. 23, 01.06.2017, p. 6440-6444.

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

Kirberger, SE, Maltseva, SD, Manulik, JC, Einstein, SA, Weegman, BP, Garwood, M & Pomerantz, WCK 2017, 'Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal ¹⁹ F MRI Agents', Angewandte Chemie - International Edition, vol. 56, no. 23, pp. 6440-6444. https://doi.org/10.1002/anie.201700426

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