Sequence-Scrambling Fragmentation Pathways of Protonated Peptides.
The gas-phase structures and fragmentation pathways of the N-terminal b and a fragments of YAGFL-NH, AGLFY-NH, GFLYA-NH, FLYAG-NH, and LYAGF-NH were investigated using collision-induced dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. Our combined...
| Publicado en: | Journal of the American Chemical Society Vol. 130; no. 52; pp. 17774 - 17790 |
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| Autores principales: | , , , , , , |
| Formato: | Artículo |
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American Chemical Society
12/31/2008
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| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=35946336&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 35946336 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 12/31/2008 vid: 130 iid: 52 pid: 997 pub: American Chemical Society artinfo: ui: 35946336 10.1021/ja805074d ppf: 17774 ppct: 16 formats: tig: atl: Sequence-Scrambling Fragmentation Pathways of Protonated Peptides. aug: au: Bleiholder, Christian Osburn, Sandra Williams, Todd D. Suhai, Sándor Van Stipdonk, Michael Harrison, Alex G. Paizs, Béla affil: Department of Molecular Biophysics, Im Neuenheimer Feld 580, German Cancer Research Center, 69120 Heidelberg, Germany Department of Chemistry, Wichita State University, Wichita, Kansas 67260 Molecular Structures Group, Department of Chemistry, University of Kansas, Lawrence, Kansas 66045 Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada su: Chemistry Density functionals Ions Peptides Electrons Nuclear isomers sug: subj: Chemistry Density functionals Ions Peptides Electrons Nuclear isomers ab: The gas-phase structures and fragmentation pathways of the N-terminal b and a fragments of YAGFL-NH, AGLFY-NH, GFLYA-NH, FLYAG-NH, and LYAGF-NH were investigated using collision-induced dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. Our combined experimental and theoretical approach allows probing of the scrambling and rearrangement reactions that take place in CID of b and a ions. It is shown that low-energy CID of the b fragments of the above peptides produces nearly the same dissociation patterns. Furthermore, CID of protonated cyclo-(YAGFL) generates the same fragments with nearly identical ion abundances when similar experimental conditions are applied. This suggests that rapid cyclization of the primarily linear b ions takes place and that the CID spectrum is indeed determined by the fragmentation behavior of the cyclic isomer. This can open up at various amide bonds, and its fragmentation behavior can be understood only by assuming a multitude of fragmenting linear structures. Our computational results fully support this cyclization-reopening mechanism by showing that protonated cyclo-(YAGFL) is energetically favored over the linear b isomers. Furthermore, the cyclization-reopening transition structures are energetically less demanding than those of conventional bond-breaking reactions, allowing fast interconversion among the cyclic and linear isomers. This chemistry can lead in principle to complete loss of sequence information upon CID, as documented for the b ion of FLYAG-NH. CID of the a ions of the above peptides produces fragment ion distributions that can be explained by assuming b-type scrambling of their parent population and a → a*-type rearrangement pathways ( Vachet, R. W., Bishop, B. M., Erickson, B. W., and Glish, G. L. J. Am. Chem. Soc. 1997, 119, 5481). While a ions easily undergo cyclization, the resulting macrocycle predominantly reopens to regenerate the original linear structure. Computational data indicate that the a → a*-type rearrangement pathways of the linear a isomers involve post-cleavage proton-bound dimer intermediates in which the fragments reassociate and the originally C-terminal fragment is transferred to the N-terminus. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2008 holdings: @attributes: islocal: N |
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