Synthesis of fluorinated leucines, valines and alanines for use in protein NMR?

Organic & Biomolecular Chemistry Pub Date: 2022-03-04 DOI: 10.1039/D2OB00145D

Abstract

Efficient syntheses of fluorinated leucines, valines and alanines are described. The synthetic routes provide expedient access to various 13C/15N/D isotopologues requiring solely readily available and inexpensive isotope containing reagents such as NaBD4, carbon-13C dioxide and sodium azide-1-15N. The lightly fluorinated leucines and valines were found to be good substrates for cell-free protein expression and even 3-fluoroalanine, which is highly toxic to bacteria in vivo, could be incorporated into proteins this way. 19F-NMR spectra of the protein GB1 produced with these amino acids showed large chemical shift dispersions. Particularly high incorporation yields and clean 19F-NMR spectra were obtained for GB1 produced with valine residues, which had been synthesized with a single fluorine substituting a hydrogen stereospecifically in one of the methyl groups.

Graphical abstract: Synthesis of fluorinated leucines, valines and alanines for use in protein NMR
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