A Facile Method for Separation of the Cryptic Methionine Sulfoxide Diastereomers, Structural Assignment and DFT Analysis
Abstract
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 CO₂ chromatography and allows obtaining both diastereomers in purities exceeding 99 %. ¹H 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.
Additional Information
© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. Issue Online: 06 April 2020; Version of Record online: 06 February 2020; Accepted manuscript online: 22 December 2019; Manuscript revised: 18 December 2019; Manuscript received: 24 October 2019. J.A.R. thanks UCSC for flexible start‐up funds and a special research grant to study methionine oxidation. Dr. Indranil Chakraborty is gratefully acknowledged for assistance at early stages of the project. We also thank the late Mr. Stephen Hauskins and the UCSC computing team for help and support. The authors declare no conflict of interest.Attached Files
Accepted Version - Raskatov_et_al-2019-Chemistry_-_A_European_Journal.pdf
Supplemental Material - chem201904848-s1-accepted_meto_si.docx
Supplemental Material - chem201904848-sup-0001-misc_information.pdf
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Additional details
- Eprint ID
- 100492
- Resolver ID
- CaltechAUTHORS:20200103-100613520
- University of California, Santa Cruz
- Created
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2020-01-05Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field