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Identification of aspartic and isoaspartic acid residues in amyloid beta peptides, including A beta 1-42, using electron-ion reactions
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Sargaeva, Nadezda P., Lin, Cheng and O'Connor, Peter B. (2009) Identification of aspartic and isoaspartic acid residues in amyloid beta peptides, including A beta 1-42, using electron-ion reactions. Analytical Chemistry, Vol.81 (No.23). pp. 9778-9786. doi:10.1021/ac901677t
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Official URL: http://dx.doi.org/10.1021/ac901677t
Abstract
Amyloid beta peptides are the major components of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease (AD). Although it is still unclear what initiates the disease, isomerization of aspartic acid residues in A beta peptides is directly related to the pathology of AD. The detection of isomerization products is analytically challenging, due to their similar chemical properties and identical molecular mass. Different methods have been applied to differentiate and quantify the isomers, including immunology, chromatography, and mass spectrometry. Typically, those methods require comparative analysis with the standard peptides and involve many sample preparation steps. To understand the role of A beta isomerization in AD progression, a fast, simple, accurate, and reproducible method is necessary. In this work, electron capture dissociation (ECD) Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS) was applied to detect isomerization in A beta peptides. ECD generated diagnostic fragment ions for the two isomers of A beta 17-28, [M + 2H - 60](+center dot) and z(6)(center dot) - 44 when aspartic acid was present and z(6)(center dot) - 57 when isoaspartic acid was present. Additionally, the z. - 57 diagnostic ion was also observed in the electron ionization dissociation (EID) spectra of the modified A beta 17-28 fragment. ECD was further applied toward A beta 1-40 and A beta 1-42. The diagnostic ion c(6) + 57 was observed in the ECD spectra of the A beta 1 - 42 peptide, demonstrating isomerization at residue 7. In conclusion, both ECD and EID can clearly determine the presence and the position of isoaspartic acid residues in amyloid beta peptides. The next step, therefore, is to apply this method to analyze samples of Alzheimer's patients and healthy individuals in order to generate a better understanding of the disease.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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| Divisions: | Faculty of Science > Chemistry | ||||
| Library of Congress Subject Headings (LCSH): | High performance liquid chromatography, Multiply charged ions, Tandem mass spectrometry, Amyloid beta-protein, Electron-ion collisions, Deamination, Isomerization, Aspartic acid, Isoaspartic acid | ||||
| Journal or Publication Title: | Analytical Chemistry | ||||
| Publisher: | American Chemical Society | ||||
| ISSN: | 0003-2700 | ||||
| Official Date: | 1 December 2009 | ||||
| Dates: |
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| Volume: | Vol.81 | ||||
| Number: | No.23 | ||||
| Number of Pages: | 9 | ||||
| Page Range: | pp. 9778-9786 | ||||
| DOI: | 10.1021/ac901677t | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | National Center for Research Resources (U.S.) (NCRR), National Institutes of Health (U.S.) (NIH), National Heart, Lung, and Blood Institute (NHLBI), National Institute of General Medical Sciences (U.S.) (NIGMS) | ||||
| Grant number: | P41 RR10888 (NIH/NCRR), N01HV28178 (NIH/NHLBI), R01GM078293 (NIH/NIGMS) |
Data sourced from Thomson Reuters' Web of Knowledge
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