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.
Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, Wroclaw, Poland.
Remigiusz
R
Bąchor
Bartosz
B
Setner
Alicja
A
Kluczyk
Piotr
P
Stefanowicz
Zbigniew
Z
Szewczuk
D002244:Carbon / Q000737:chemistry*; D003903:Deuterium / Q000737:chemistry*; D041961:Deuterium Exchange Measurement; D005998:Glycine / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011522:Protons; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
D010455:Peptides; D011522:Protons; D002244:Carbon; D003903:Deuterium; D005998:Glycine
ESI-MS/MS; HDX of peptides; cyclosporine; hydrogen scrambling; sarcosine