Composite Multidimensional Ion Mobility-Mass Spectrometry for Improved Differentiation of Stereochemical Modifications

Overview

Journal Anal Chem

Specialty Chemistry

Date 2023 Jan 12

PMID 36635260

Authors

Xia Xu

Li Han

Zhen Zheng

Rui Zhao

Lingjun Li

Xueguang Shao

Gongyu Li

Affiliations

Soon will be listed here.

Abstract

Stereochemical modifications (SCMs), mostly present in the form of d-amino acid substitution, have been increasingly identified from a wide range of neuropeptides and disease-associated biomarker proteins. Traditional mass spectrometry-based SCM identification has been effectively enhanced with technological and strategic advancements in ion mobility spectrometry. With the additional separation provided by ion mobility, SCM-induced structural changes can be probed both in theory and in practice, although the structural resolution for low-abundance SCMs still requires further improvement to enable accurate quantification or unambiguous identification of stereoisomers. Herein, we present a multi-component-enabled multidimensional ion mobility-mass spectrometry (3M-IM-MS) analytical workflow, based upon the metal-enhanced chiral amplification strategy we proposed previously (, 2019, 5038). Notably, the 3M-IM-MS strategy comprises and features the powerful mathematical tools of continuous wavelet transform and Gaussian fitting-enabled peak splitting. Consequently, the resolving capability of ion mobility spectrometry for SCM analysis has been significantly enhanced, providing mobility profiles with baseline separation and more than fivefold improvement in resolving power and overall resolution. This study represents an alternative toward ultrahigh-resolution structural interrogation of mixtures with very small differences, featuring an important and long-lasting topic in chemical measurement.

Citing Articles

Site-specific chirality-conferred structural compaction differentially mediates the cytotoxicity of Aβ42.

Li G, Jeon C, Ma M, Jia Y, Zheng Z, Delafield D Chem Sci. 2023; 14(22):5936-5944.

PMID: 37293657 PMC: 10246695. DOI: 10.1039/d3sc00678f.

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