Design of Highly Fluorinated Peptides for Cell-based 19F NMR

Jiaqian Li, Steven E Kirberger, Yiao Wang, Huarui Cui, Carston R. Wagner, William C.K. Pomerantz

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The design of imaging agents with high fluorine content is essential for overcoming the challenges associated with signal detection limits in 19F MRI-based molecular imaging. In addition to perfluorocarbon and fluorinated polymers, fluorinated peptides offer an additional strategy for creating sequence-defined 19F magnetic resonance imaging (MRI) imaging agents with a high fluorine signal. Our previously reported unstructured trifluoroacetyllysine-based peptides possessed good physiochemical properties and could be imaged at high magnetic field strength. However, the low detection limit motivated further improvements in the fluorine content of the peptides as well as removal of nonspecific cellular interactions. This research characterizes several new highly fluorinated synthetic peptides composed of highly fluorinated amino acids. 19F NMR analysis of peptides TB-1 and TB-9 led to highly overlapping, intense fluorine resonances and acceptable aqueous solubility. Flow cytometry analysis and fluorescence microscopy further showed nonspecific binding could be removed in the case of TB-9. As a preliminary experiment toward developing molecular imaging agents, a fluorinated EGFR-targeting peptide (KKKFFKK-βA-YHWYGYTPENVI) and an EGFR-targeting protein complex E1-DD bioconjugated to TB-9 were prepared. Both bioconjugates maintained good 19F NMR performance in aqueous solution. While the E1-DD-based imaging agent will require further engineering, the success of cell-based 19F NMR of the EGFR-targeting peptide in A431 cells supports the potential use of fluorinated peptides for molecular imaging.

Original languageEnglish (US)
Pages (from-to)1477-1485
Number of pages9
JournalBioconjugate Chemistry
Volume34
Issue number8
DOIs
StatePublished - Aug 16 2023

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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