Separation of ß-Amyloid Tryptic Peptide Species with Isomerized and Racemized L-Aspartic Residues with Ion Mobility in Structures for Lossless Ion Manipulations

Journal Article · Tue Apr 02 00:00:00 EDT 2019 · Analytical Chemistry

DOI:https://doi.org/10.1021/acs.analchem.8b04696· OSTI ID:1525291

Nagy, Gavril ^[1]; Kedia, Komal ^[1]; Attah, Isaac K. ^[1]; Garimella, Venkata BS  ^[1]; Ibrahim, Yehia M.  ^[1]; Petyuk, Vladislav A.  ^[1]; Smith, Richard D.  ^[1]

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1. BATTELLE (PACIFIC NW LAB)

Accumulation of ß-amyloid (Aß) is one of the hallmarks of Alzheimer’s disease. The deposition of ß-amyloid plaques is likely to start years in advance of manifestation of clinical symptoms, although the exact timing is unknown. Over the years, Aß peptides undergo post-translational modifications and stereoisomerization. Analysis of stereoisomers is particularly challenging due to their identical elemental composition and similar physicochemical properties. Herein we have utilized our recently developed structures for lossless ion manipulations ion mobility-mass spectrometry platform (SLIM IM-MS), in conjunction with SLIM serpentine ultralong path with extended routing (SUPER), to baseline resolve four distinct sets of Aß17-28 tryptic peptide epimers on a rapid (~1 second) timescale. We discovered that sodium adduct ions, [M+H+Na]2+, allowed baseline IM resolution for all Aß epimer sets assessed, while such baseline separations were unachievable for their [M+2H]2+ doubly protonated ions.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1525291
• Report Number(s): PNNL-SA-138885
• Journal Information: Analytical Chemistry, Vol. 91, Issue 7
• Country of Publication: United States
• Language: English