title: Application of electron transfer dissociation mass spectrometry in analyses of non-enzymatically glycated peptides.
abstract: Non-enzymatic glycation of peptides and proteins by D-glucose has important implications in the pathogenesis of diabetes mellitus, particularly in the context of development of diabetic complications. The fragmentation behavior of glycated peptides produced from reaction of D-glucose with lysine residues was investigated by electron transfer dissociation (ETD) and collision-induced dissociation (CID) tandem mass spectrometry. It was found that high abundance ions corresponding to various degrees of neutral water losses, as well as furylium ion production, dominate the CID spectra, and that the sequence-informative b and y ions were rarely observed when Amadori-modified peptides were fragmented. Contrary to what was observed under CID conditions, ions corresponding to neutral losses of water or furylium ion production were not observed in the ETD spectra. Instead, abundant and almost complete series of c- and z-type ions were observed regardless of whether the modification site was located in the middle of the sequence or close to the N-terminus, greatly facilitating the peptide sequencing. This study strongly suggests that ETD is a better technique for proteomic studies of non-enzymatically glycated peptides and proteins.
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Andrej
authors.initials: A
authors.lastname: Frolov
authors.forename: Ning
authors.initials: N
authors.lastname: Tang
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Tom
authors.initials: T
authors.lastname: van de Goor
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
mesh_terms: D004583:Electrons; D005947:Glucose / Q000737:chemistry; D006031:Glycosylation; D008239:Lysine / Q000737:chemistry; D010449:Peptide Mapping; D010455:Peptides / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D010455:Peptides; D005947:Glucose; D008239:Lysine