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Characterizing ion mobility-mass spectrometry conformation space for the analysis of complex biological samples

Abstract

The conformation space occupied by different classes of biomolecules measured by ion mobility-mass spectrometry (IM-MS) is described for utility in the characterization of complex biological samples. Although the qualitative separation of different classes of biomolecules on the basis of structure or collision cross section is known, there is relatively little quantitative cross-section information available for species apart from peptides. In this report, collision cross sections are measured for a large suite of biologically salient species, including oligonucleotides (n = 96), carbohydrates (n = 192), and lipids (n = 53), which are compared to reported values for peptides (n = 610). In general, signals for each class are highly correlated, and at a given mass, these correlations result in predicted collision cross sections that increase in the order oligonucleotides < carbohydrates < peptides < lipids. The specific correlations are described by logarithmic regressions, which best approximate the theoretical trend of increasing collision cross section as a function of increasing mass. A statistical treatment of the signals observed within each molecular class suggests that the breadth of conformation space occupied by each class increases in the order lipids < oligonucleotides < peptides < carbohydrates. The utility of conformation space analysis in the direct analysis of complex biological samples is described, both in the context of qualitative molecular class identification and in fine structure examination within a class. The latter is demonstrated in IM-MS separations of isobaric oligonucleotides, which are interpreted by molecular dynamics simulations.

Potential for performing simultaneous “omics” through the separation of biomolecular classes on the basis of structure and mass using ion mobility-mass spectrometry

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Acknowledgments

Financial support for this work was provided by the National Institutes of Health (via NIDA subcontracts HHSN271200800020C, HHSN271200700012C and a subcontract via NCRR grant 5R44RR020238-03 with Ionwerks, Inc.), Vanderbilt University College of Arts and Sciences, Vanderbilt Institute of Chemical Biology, the American Society for Mass Spectrometry (Research award to J.A.M), and the Spectroscopy Society of Pittsburgh. The carbohydrate compounds Gala3-type1, P1, H-type2-LN-LN, P1 antigen-sp, Di-LeA, P1 penta, LNT, Lec-Lec, Tri-LacNAc, GNLNLN, and 3′SLN-Lec were provided by the Carbohydrate Synthesis/Protein Expression Core of the Consortium for Functional Glycomics funded by the National Institute of General Medical Sciences grant GM62116.

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Correspondence to John A. McLean.

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Fenn, L.S., Kliman, M., Mahsut, A. et al. Characterizing ion mobility-mass spectrometry conformation space for the analysis of complex biological samples. Anal Bioanal Chem 394, 235–244 (2009). https://doi.org/10.1007/s00216-009-2666-3

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  • DOI: https://doi.org/10.1007/s00216-009-2666-3

Keywords

  • Ion mobility
  • Ion mobility-mass spectrometry
  • Mass spectrometry
  • Collision cross section
  • Conformation space
  • Oligonucleotides
  • Carbohydrates
  • Peptides
  • Lipids