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 journalArticlepeer-review

19 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 languageEnglish (US)
Pages (from-to)6440-6444
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number23
DOIs
StatePublished - 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

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • F NMR spectroscopy
  • fluorination
  • magnetic resonance imaging
  • molecular imaging
  • peptides

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