The synthesis of specifically isotope labelled fluorotryptophan and its use in mammalian cell-based protein expression for 19F-NMR applications

Chem Commun (Camb). 2024 Nov 28;60(96):14188-14191. doi: 10.1039/d4cc04789c.

Abstract

19F nuclei serve as versatile sensors for detecting protein interactions and dynamics in biomolecular NMR spectroscopy. Although various methods have been developed to incorporate fluorine-containing aromatic residues into proteins using E. coli or cell-free expression techniques, similar approaches for protein production in mammalian cell lines remain limited. Here, we present a cost-effective synthetic route to obtain selectively deuterated, carbon-13 labeled fluorotryptophan and demonstrate its use in introducing 19F-13C spin pairs into carbonic anhydrase 2 and superoxide dismutase, following an expression protocol utilizing HEK cells.

MeSH terms

  • Carbon Isotopes / chemistry
  • Carbonic Anhydrase II* / metabolism
  • Fluorine* / chemistry
  • HEK293 Cells
  • Humans
  • Isotope Labeling*
  • Nuclear Magnetic Resonance, Biomolecular
  • Superoxide Dismutase / metabolism
  • Tryptophan* / analogs & derivatives
  • Tryptophan* / chemical synthesis
  • Tryptophan* / chemistry
  • Tryptophan* / metabolism

Substances

  • Tryptophan
  • Fluorine
  • Carbonic Anhydrase II
  • Superoxide Dismutase
  • Carbon Isotopes
  • Carbon-13