The unusual hydrogen‐deuterium exchange of α ‐carbon protons in N ‐substituted glycine‐containing peptides

Hydrogens connected to α ‐carbon ( α ‐C) of amino acid residues are usually resistant to hydrogen‐deuterium exchange (HDX) unless reaction conditions promote racemization. Although N ‐methylglycine (sarcosine) residue has been found in biologically active peptide such as cyclosporine, to the best of our knowledge, the HDX of α ‐C protons of this residue was not explored yet. Here, we presented a new and efficient methodology of α ‐C deuteration in sarcosine residues under basic aqueous conditions. The deuterons, introduced at α ‐C atom, do not undergo back‐exchange in acidic aqueous solution. The electrospray ionization‐MS and MS/MS experiments on proposed model peptides confirmed the HDX at α ‐C and revealed the unexpected hydrogen scrambling in sarcosine‐containing peptides. Although the observed HDX of α ‐C protons is only successful in N ‐acylglycine when the amide possesses a certain degree of alkylation, it offers a new approach to the analysis of sarcosine‐containing peptides such as cyclosporine. Copyright © 2014 John Wiley & Sons, Ltd.