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A Facile Method for the Separation of Methionine Sulfoxide Diastereomers, Structural Assignment, and DFT Analysis
Author(s) -
Raskatov Jevgenij A.,
Virgil Scott,
Lee HsiauWei,
Henling Lawrence M.,
Chan Ka,
Kuhn Ariel J.,
Foley Alejandro R.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201904848
Subject(s) - diastereomer , methionine , chemistry , sulfur , chirality (physics) , methionine sulfoxide , sulfoxide , redox , amino acid , combinatorial chemistry , stereochemistry , organic chemistry , biochemistry , quark , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics
Methionine (Met) oxidation is an important biological redox node, with hundreds if not thousands of protein targets. The process yields methionine oxide (MetO). It renders the sulfur chiral, producing two distinct, diastereomerically related products. Despite the biological significance of Met oxidation, a reliable protocol to separate the resultant MetO diastereomers is currently lacking. This hampers our ability to make peptides and proteins that contain stereochemically defined MetO to then study their structural and functional properties. We have developed a facile method that uses supercritical CO 2 chromatography and allows obtaining both diastereomers in purities exceeding 99 %. 1 H NMR spectra were correlated with X‐ray structural information. The stereochemical interconversion barrier at sulfur was calculated as 45.2 kcal mol −1 , highlighting the remarkable stereochemical stability of MetO sulfur chirality. Our protocol should open the road to synthesis and study of a wide variety of stereochemically defined MetO‐containing proteins and peptides.