Dual Source Ion Mobility-Mass Spectrometer for Direct Comparison of Electrospray Ionization and MALDI Collision Cross Section Measurements

Sundarapandian, Sevugarajan; May, Jody C.; McLean, John A.

doi:10.1021/ac902980r

Cited by 25 publications

(18 citation statements)

References 44 publications

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“…Peptide CCS measurements are reported in Table 1. The peptide natural products were prepared and analyzed using a MALDI-IM-MS instrument which was described previously, 10 and further information about the sample preparation and collision cross section calculations can be found in the Experimental Section below. The collision cross sections for all of the quasimolecular ions present ( i.e.…”

Section: Resultsmentioning

confidence: 99%

Structural Mass Spectrometry: Rapid Methods for Separation and Analysis of Peptide Natural Products

et al. 2012

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A significant challenge in natural product discovery is the initial discrimination of discrete secondary metabolites alongside functionally similar primary metabolic cellular components within complex biological samples. A property that has yet to be fully exploited for natural product identification and characterization is the gas phase collision cross section, or, more generally, the mobility-mass correlation. Peptide natural products possess many of the properties that distinguish natural products as they are frequently characterized by a high degree of intramolecular bonding, and possess extended and compact conformations among other structural modifications. This report describes a rapid structural mass spectrometry technique based on ion mobility-mass spectrometry for the comparison of peptide natural products to their primary metabolic congeners using mobility-mass correlation. This property is empirically determined using ion mobility-mass spectrometry, applied to the analysis of linear versus modified peptides, and used to discriminate peptide natural products in a crude microbial extract. Complementary computational approaches are utilized to understand the structural basis for the separation of primary metabolism derived linear peptides from secondary metabolite cyclic and modified cyclic species. These findings provide a platform for enhancing the identification of secondary metabolic peptides with distinct mobility-mass ratios within complex biological samples.

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Section: Resultsmentioning

confidence: 99%

Structural Mass Spectrometry: Rapid Methods for Separation and Analysis of Peptide Natural Products

et al. 2012

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“…Additionally, we have also measured the CCS of all charge states except the [M + 2H] 2+ using a low‐resolution ( t /Δ t of ca . 20) drift tube instrument, which has been described previously . A comparison of these measurements is provided in Fig.…”

Section: Discussionmentioning

confidence: 99%

A uniform field ion mobility study of melittin and implications of low‐field mobility for resolving fine cross‐sectional detail in peptide and protein experiments

May

McLean

2015

Proteomics

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An experimental investigation of protonated melittin was undertaken using uniform field ion mobility-mass spectrometry (IM-MS) to measure helium-based collision cross sections (CCS). Upon varying the electrospray solvent from aqueous to methanol, the [M + 2H](2+) species was observed to shift from a compact to an extended CCS, suggesting a gas-phase structural transition which depends on initial solvent conditions. The [M + 3H](3+), [M + 4H](4+), and [M + 5H](5+) species exhibited peak broadening in response to the organic solvent, but retained their CCS, suggesting these are locked into a stable gas-phase structure. The CCS of the stable [M + 3H](3+) and [M + 4H](4+) species were found to be similar, suggesting these ions adopt structurally similar features in the gas phase, which, based on previous studies, likely retains α-helical characteristics. We also report on the resolution of additional low-abundance ion mobility peak features which are sensitive to the magnitude of the drift field. We observe a loss in the peptide ion mobility resolution above ca. eight Townsends, suggesting that the ability to resolve subtle structural details is inherently related to conducting ion mobility measurements at low field and under conditions which minimize ion heating.

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“…Further experimental and instrumentation details have been presented previously in the literature. 4 , 38 …”

Section: Methodsmentioning

confidence: 99%

Distance Geometry Protocol to Generate Conformations of Natural Products to Structurally Interpret Ion Mobility-Mass Spectrometry Collision Cross Sections

et al. 2014

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Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data.

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Dual Source Ion Mobility-Mass Spectrometer for Direct Comparison of Electrospray Ionization and MALDI Collision Cross Section Measurements

Cited by 25 publications

References 44 publications

Structural Mass Spectrometry: Rapid Methods for Separation and Analysis of Peptide Natural Products

Structural Mass Spectrometry: Rapid Methods for Separation and Analysis of Peptide Natural Products

A uniform field ion mobility study of melittin and implications of low‐field mobility for resolving fine cross‐sectional detail in peptide and protein experiments

Distance Geometry Protocol to Generate Conformations of Natural Products to Structurally Interpret Ion Mobility-Mass Spectrometry Collision Cross Sections

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