title: Convenient preparation of deuterium-labeled analogs of peptides containing N-substituted glycines for a stable isotope dilution LC-MS quantitative analysis.
abstract: N-substituted glycines constitute mimics of natural amino acids that are of great interest in the peptide-based drug development. Peptoids-oligo(N-substituted glycines) have been recently demonstrated to be highly active peptidomimetics in biological systems, resistant to proteolytic degradation. We developed a method of the deuterium labeling of peptidomimetics containing N-substituted glycine residues via H/D exchange of their α-carbon hydrogen atoms. The labeling was shown to be easy, inexpensive, and without the use of derivatization reagents or the need for a further purification. The deuterons introduced at the α-carbon atoms do not undergo a back exchange under acidic conditions during liquid chromatography mass spectrometry (LC-MS) analysis. The LC-MS analysis of a mixture of isotopologues revealed a co-elution of deuterated and nondeuterated forms of the peptidomimetics, which may be useful in the quantitative isotope dilution analysis of peptoids and other derivatives of N-substituted glycines.
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383, Wroclaw, Poland.
authors.forename: Remigiusz
authors.initials: R
authors.lastname: Bąchor
authors.affiliation: Faculty of Chemistry, Gdansk University, Wita Stwosza 63, 80-952, Gdansk, Poland.
authors.forename: Dawid
authors.initials: D
authors.lastname: Dębowski
authors.affiliation: Faculty of Chemistry, Gdansk University, Wita Stwosza 63, 80-952, Gdansk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Łęgowska
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Stefanowicz
authors.affiliation: Faculty of Chemistry, Gdansk University, Wita Stwosza 63, 80-952, Gdansk, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Rolka
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383, Wroclaw, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Szewczuk
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003553:Cystine; D003903:Deuterium; D041961:Deuterium Exchange Measurement; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D007201:Indicator Dilution Techniques; D007553:Isotope Labeling; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D034444:Peptoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry; D053719:Tandem Mass Spectrometry
chemical_list: D010455:Peptides; D034444:Peptoids; D003553:Cystine; D003903:Deuterium; D005998:Glycine
keywords: ESI-MS; HDX of peptides; peptoids; peptomers; quantitative analysis