Probing High-Order Transient Oligomers Using Ion Mobility Mass Spectrometry Coupled with Infrared Action Spectroscopy

Sjors Bakels, Steven Daly, Berk Doğan, Melissa Baerenfaenger, Jan Commandeur, Anouk M. Rijs*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Understanding and controlling peptide aggregation are critical due to its neurotoxic implications. However, structural information about the key intermediates, the oligomers, is obscured by a cascade of coinciding events occurring at various time and energy scales, which results in complex and heterogeneous mixtures of oligomers. To address this challenge, we have developed the Photo-Synapt, a novel, multidimensional spectrometer that integrates ion mobility mass spectrometry with infrared (IR) action spectroscopy within a single experiment. By combining three different orthogonal analytical dimensions, we can select and isolate individual oligomers by mass, charge, size, and shape and provide a unique molecular fingerprint for each oligomer. The broad application of this technology is demonstrated by its application to oligosaccharide analysis from glycoproteins, which are challenging to analyze due to the minute differences between isomers. By integration of IR action spectroscopy with ion mobility mass spectrometry, this approach adds an analytical dimension that effectively addresses this limitation, offering a unique molecular fingerprint for each isomer.

Original languageEnglish
Pages (from-to)13962-13970
Number of pages9
JournalAnalytical chemistry
Volume96
Issue number34
Early online date16 Aug 2024
DOIs
Publication statusPublished - 27 Aug 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.

Funding

The authors gratefully acknowledge funding from the research program VICI with project number VI.C.192.024 and Aspasia (015.015.009) from the Dutch Research Council (NWO) awarded to A.M.R. We would like to thank all members from the MS-Laserlab (Vrije Universiteit Amsterdam), and especially Iuliia Stroganova, Agathe Depraz Depland and Kevin Hes, for helpful discussions.

FundersFunder number
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

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