Ion Mobility Spectrometry-Mass Spectrometry Coupled with Gas-Phase Hydrogen/Deuterium Exchange for Metabolomics Analyses

Ion mobility spectrometry-mass spectrometry (IMS-MS) in combination with gas-phase hydrogen/deuterium exchange (HDX) and collision-induced dissociation (CID) is evaluated as an analytical method for small-molecule standard and mixture characterization. Experiments show that compound ions exhibit unique HDX reactivities that can be used to distinguish different species. Additionally, it is shown that gas-phase HDX kinetics can be exploited to provide even further distinguishing capabilities by using different partial pressures of reagent gas. The relative HDX reactivity of a wide variety of molecules is discussed in light of the various molecular structures. Additionally, hydrogen accessibility scoring (HAS) and HDX kinetics modeling of candidate (in silico) ion structures is utilized to estimate the relative ion conformer populations giving rise to specific HDX behavior. These data interpretation methods are discussed with a focus on developing predictive tools for HDX behavior. Finally, an example is provided in which ion mobility information is supplemented with HDX reactivity data to aid identification efforts of compounds in a metabolite extract.

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Copper,gold, and silver decorated magnetic core–polymeric shell nanostructures for destruction of pathogenic bacteria

Fe₃O₄ magnetic nanoparticles (MNPs) were prepared by co-precipitation method. The nanoparticles were silica coated using TEOS, and then modified by the polymeric layers of polypropylene glycol (PPG) and polyethylene glycol (PEG). Finally, the core-shell samples were decorated with Ag, Au, and Cu nanoparticles. The products were characterized by vibrating sample magnetometry (VSM), TGA, SEM, XRD, and FTIR methods. The antibacterial activity of the prepared samples was evaluated in inactivation of E. coli and S. aureus microorganisms, representing the Gram-negative and Gram-positive species, respectively. The effect of solid dosage, bacteria concentration and type of polymeric modifier on the antibacterial activity was investigated. TEM images of the bacteria were recorded after the treatment time and according to the observed changes in the cell wall, the mechanism of antibacterial action was discussed. The prepared nanostructures showed high antibacterial activity against both Gram-negative and Gram-positive bacteria. This was due to the leaching of metal ions which subsequently led to the lysis of bacteria. A theoretical investigation was also done by studying the interaction of loaded metals with the nucleotide components of the microorganism DNA, and the obtained results were used to explain the experimental data. Finally, based on the observed inactivation curves, we explain the antibacterial behavior of the prepared nanostructures mathematically.

     

Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics

The first 17 amino acid residues of Huntingtin protein (Nt17 of htt) are thought to play an important role in the protein's function; Nt17 is one of two membrane binding domains in htt. In this study the binding ability of Nt17 peptide with vesicles comprised of two subclasses of phospholipids is studied using electrospray ionization ‐ mass spectrometry (ESI‐MS) and molecular dynamics (MD) simulations. Overall, the peptide is shown to have a greater propensity to interact with vesicles of phosphatidylcholine (PC) rather than phosphatidylethanolamine (PE) lipids. Mass spectra show an increase in lipid‐bound peptide adducts where the ordering of the number of such specie is 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC) > 1‐palmitoyl‐2‐oleoyl‐glycero‐3‐phosphocholine (POPC) > 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3 phosphoethanolamine (POPE). MD simulations suggest that the compactness of the bilayer plays a role in governing peptide interactions. The peptide shows greater disruption of the DOPC bilayer order at the surface and interacts with the hydrophobic tails of lipid molecules via hydrophobic residues. Conversely, the POPE vesicle remains ordered and lipids display transient interactions with the peptide through the formation of hydrogen bonds with hydrophilic residues. The POPC system displays intermediate behavior with regard to the degree of peptide‐membrane interaction. Finally, the simulations suggest a helix stabilizing effect resulting from the interactions between hydrophobic residues and the lipid tails of the DOPC bilayer.     

Comparison of Peptide Ion Conformers Arising from Non-Helical and Helical Peptides Using Ion Mobility Spectrometry and Gas-Phase Hydrogen/Deuterium Exchange

The dominant gas-phase conformer of [M+3H]³⁺ ions of the model peptide acetyl-PSSSSKSSSSKSSSSKSSSSK has been examined with ion mobility spectrometry (IMS), gas-phase hydrogen deuterium exchange (HDX), and mass spectrometry (MS) techniques. The [M+3H]³⁺ peptide ions are observed predominantly as a relatively compact conformer type. Upon subjecting these ions to electron transfer dissociation (ETD), the level of protection for each amino acid residue in the peptide sequence is assessed. The overall per-residue deuterium uptake is observed to be relatively more efficient for the neutral residues than for the model peptide acetyl-PAAAAKAAAAKAAAAKAAAAK. In comparison, the N-terminal and C-terminal regions of the serine peptide show greater relative protection compared with interior residues. Molecular dynamics (MD) simulations have been used to generate candidate structures for collision cross section and HDX reactivity matching. Hydrogen accessibility scoring (HAS) for select structural candidates from MD simulations has been used to suggest conformer types that could contribute to the observed HDX patterns. The results are discussed with respect to recent studies employing extensive MD simulations of gas-phase structure establishment of a peptide system.

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