title: Estimation of peptide N-Cα bond cleavage efficiency during MALDI-ISD using a cyclic peptide.
abstract: Matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) induces N-Cα bond cleavage via hydrogen transfer from the matrix to the peptide backbone, which produces a c'/z• fragment pair. Subsequently, the z• generates z' and [z + matrix] fragments via further radical reactions because of the low stability of the z•. In the present study, we investigated MALDI-ISD of a cyclic peptide. The N-Cα bond cleavage in the cyclic peptide by MALDI-ISD produced the hydrogen-abundant peptide radical [M + 2H](+) • with a radical site on the α-carbon atom, which then reacted with the matrix to give [M + 3H](+) and [M + H + matrix](+) . For 1,5-diaminonaphthalene (1,5-DAN) adducts with z fragments, post-source decay of [M + H + 1,5-DAN](+) generated from the cyclic peptide showed predominant loss of an amino acid with 1,5-DAN. Additionally, MALDI-ISD with Fourier transform-ion cyclotron resonance mass spectrometry allowed for the detection of both [M + 3H](+) and [M + H](+) with two (13) C atoms. These results strongly suggested that [M + 3H](+) and [M + H + 1,5-DAN](+) were formed by N-Cα bond cleavage with further radical reactions. As a consequence, the cleavage efficiency of the N-Cα bond during MALDI-ISD could be estimated by the ratio of the intensity of [M + H](+) and [M + 3H](+) in the Fourier transform-ion cyclotron resonance spectrum. Because the reduction efficiency of a matrix for the cyclic peptide cyclo(Arg-Gly-Asp-D-Phe-Val) was correlated to its tendency to cleave the N-Cα bond in linear peptides, the present method could allow the evaluation of the efficiency of N-Cα bond cleavage for MALDI matrix development. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: National Metrology Institute of Japan (NMIJ), Reserch Institute for Measurement and Analytical Instrumentation, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Asakawa
authors.affiliation: Chemistry Department and GIGA-R, Mass Spectrometry Laboratory, University of Liège, Liège, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Smargiasso
authors.affiliation: Chemistry Department and GIGA-R, Mass Spectrometry Laboratory, University of Liège, Liège, Belgium.
authors.forename: Edwin
authors.initials: E
authors.lastname: De Pauw
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D006096:Gramicidin / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; C510889:1,5-diaminonaphthalene; D006096:Gramicidin; D002244:Carbon; D015081:2-Naphthylamine; D009584:Nitrogen
keywords: 1,5-diaminonaphthalene; high-resolution mass spectrometer; hydrogen attachment; lifetime of intermediate; post-source decay