A5057926336- Mass Spectrometry Techniques and Applications
- Advanced Proteomics Techniques and Applications
- Analytical Chemistry and Chromatography
- Synthesis and biological activity
- Metabolomics and Mass Spectrometry Studies
- Ion-surface interactions and analysis
- Vitamin C and Antioxidants Research
- Enzyme Structure and Function
- Electrohydrodynamics and Fluid Dynamics
- Morinda citrifolia extract uses
- Protein Structure and Dynamics
- Analytical chemistry methods development
- Diet and metabolism studies
- Protein Degradation and Inhibitors
- Crystallography and molecular interactions
- Chronic Lymphocytic Leukemia Research
- Sirtuins and Resveratrol in Medicine
- Atmospheric chemistry and aerosols
- Pesticide Residue Analysis and Safety
- Antibiotics Pharmacokinetics and Efficacy
- Click Chemistry and Applications
- Multiple Myeloma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Calpain Protease Function and Regulation
AbbVie (United States)
2014-2023
Abbott Fund
2011-2012
Indiana University Bloomington
2003-2008
Environmental Molecular Sciences Laboratory
2006
Pacific Northwest National Laboratory
2006
Purdue University West Lafayette
2002
The development of a new ion mobility/mass spectrometry instrument that incorporates multifield drift tube/ion funnel design is described. In this instrument, individual components from mixture ions can be resolved and selected on the basis mobility differences prior to collisional activation inside tube. fragment are produced dispersed again in second (IMS) region additional MS analysis. result an IMS−IMS analogue MS−MS. Here, we describe preliminary instrumental experimental approach. We...
Multidimensional ion mobility spectrometry (IMS−IMS and IMS−IMS−IMS) techniques have been combined with mass (MS) investigated as a means of generating separating peptide protein fragment ions. When fragments are generated inside drift tube then dispersed by IMS prior to MS analysis, it is possible observe many features that not apparent from analysis alone. The approach demonstrated examining fragmentation patterns arising electrospray distributions insulin chain B ubiquitin....
A new two-dimensional ion mobility spectrometry approach combined with mass has been used to examine ubiquitin ions in the gas phase. In this are separated an initial drift tube into conformation types (defined by their collision cross sections) and then a gate is introduce narrow distribution of mobility-separated second for subsequent separation. The results show that upon selection peak shape retained through tube. This requires at 300 K selected does not interconvert substantially within...
A challenge facing metabolomics in the analysis of large human cohorts is cross-laboratory comparability quantitative measurements. In this study, 14 laboratories analyzed various blood specimens using a common experimental protocol provided with Biocrates AbsoluteIDQ p400HR kit, to quantify up 408 metabolites. The included plasma and serum from male female donors, mouse rat plasma, as well NIST SRM 1950 reference plasma. metabolite classes covered range polar (e.g., amino acids biogenic...
Electrospray ionization, combined with two-dimensional ion mobility spectrometry and mass spectrometry, is used to produce, select, activate distributions of elongated ions, [M + 11H]11+ 13H]13+, ubiquitin. The analysis makes it possible examine state-to-state transitions for structural types, transition diagrams associated the efficiencies changes are presented. +11 +12 charge states can form four resolvable while only one state formed 13H]13+. Some conformations, which appear belong same...
A new quantitation method for mass spectrometry imaging (MSI) with matrix-assisted laser desorption/ionization (MALDI) has been developed. In this method, drug concentrations were determined by tissue homogenization of five 10 µm sections adjacent to those analyzed MSI. Drug levels in extracts measured liquid chromatography coupled tandem (LC/MS/MS). The integrated MSI response was correlated the LC/MS/MS determine amount detected per ion count. study reported here evaluates olanzapine liver...
A linear octopole trap interface for an ion mobility time-of-flight mass spectrometer has been developed focusing and accumulating continuous beams of ions produced by electrospray ionization. The improves experimental efficiencies factors approximately 50-200 compared with analogous configuration that utilizes a three-dimensional Paul geometry (Hoaglund-Hyzer, C. S.; Lee, Y. J.; Counterman, A. E.; Clemmer, D. E. Anal. Chem. 2002, 74, 992-1006). With these improvements, it is possible to...
Multidimensional ion mobility spectrometry techniques (IMS-IMS and IMS-IMS-IMS) combined with mass are used to study structural transitions of ubiquitin ions in the gas phase. It is possible select activate narrow distributions compact partially folded conformation types examine new structures that formed. Different conformations unfold, producing a range states three resolvable peaks associated elongated conformers. Under gentle activation conditions, final populations forms depend on...
A new ion mobility instrument that incorporates a low-field region for separation and high-field collisional activation is described. In this approach, mixtures of ions are separated based on differences in their mobilities ∼20-cm-long (∼5 V cm-1) drift tube. As the approach tube exit, they exposed to large focusing potential drop; at high fields, efficiently collisionally activated dissociate as exit We have demonstrated by examining fragmentation pattern electrosprayed bradykinin ions....
The rapid and direct analysis of the amount spatial distribution exogenous chloroquine (CHQ) CHQ metabolites from tissue sections by liquid extraction surface sampling coupled with tandem mass spectrometry (LESA‐MS/MS) was demonstrated. LESA‐MS/MS results compared well previously published quantification data collected organ excision, fluorescent detection. ability to directly sample analyze spatially resolved molecules minimal preparation analytical method development has potential...
Multidimensional separations combined with mass spectrometry are used to study the proteins that present in two states of Drosophila melanogaster: whole embryo and adult head. The approach includes incorporation a gas-phase separation dimension which ions dispersed according differences their mobilities is described as means providing detailed analytical map present. Overall, we find evidence for 1133 unique proteins. In total, 780 identified head, 660 embryo. Only 307 common both...
Two-dimensional ion mobility spectrometry (IMS-IMS) coupled with mass is examined as a means of separating mixtures tryptic peptides (from myoglobin and hemoglobin). In this study, we utilize two distinct drift regions that are identical in each contains He buffer gas at 300 K. The two-dimensional advantage realized by changing the structures ions. As ions arrive end first region, those specified selected, exposed to energizing collisions, then introduced into second region. Upon collisional...
The proteomes of three heads individual Drosophila melanogaster organisms have been analyzed and compared by a combination liquid chromatography, ion mobility spectrometry, mass spectrometry approaches. In total, 197 proteins are identified among all individuals (an average 120 ± 20 per individual), which at least 101 present in individuals. Within datasets, more than 25 000 molecular ions 9000 2000 individual) corresponding to protonated precursor peptides observed. A comparison peaks the...
Cancer cells are highly reliant on NAD+-dependent processes, including glucose metabolism, calcium signaling, DNA repair, and regulation of gene expression. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD+ salvage from nicotinamide, has been investigated as a target anticancer therapy. Known NAMPT inhibitors with potent cell activity composed nitrogen-containing aromatic group, which is phosphoribosylated by enzyme. Here, we identified two novel types...
A simple ion trap/ion mobility/time-of-flight (TOF) mass spectrometer has been coupled with nanoflow liquid chromatography to examine the feasibility of analyzing mixtures intact proteins. In this approach proteins are separated using reversed-phase chromatography. As components elute from column, they electrosprayed into gas phase and again in a drift tube prior being dispersed analyzed TOF spectrometer. The mobilities ions through buffer depend upon their collision cross sections charge...
A simple method for increasing the efficiency of multidimensional ion mobility spectrometry (IMS−IMS) measurements (as defined by number two-dimensional data sets necessary to sample all ions in a complex mixture) is illustrated. In this approach, components from packet containing mixture are introduced into first IMS drift region where they separated based on differences mobility. At exit region, narrow distributions having identical mobilities selected, subjected gentle activation...
Ion mobility measurements, combined with molecular mechanics simulations, are used to study enantiopure and racemic proline clusters formed by electrospray ionization. Broad distributions of cluster sizes charge states observed, ranging from containing only a few units that contain more than 100 (i.e., protonated the form [xPro + nH]n+ x = 1 >100 n 1−7). As increase, there is direct evidence for nanometer scale, chirally induced organization into specific structures. For 4 5, ∼50 prolines...
A field modulation approach for high-throughput ion mobility/time-of-flight analyses of complex mixtures has been developed using a split-field drift tube. In this approach, peptides, such as those that arise from tryptic digestion protein mixtures, are separated by nanocolumn liquid chromatography, ionized electrospray ionization, and analyzed techniques. The tube allows parent ions to be based on differences in their low-field mobilities through the first-field region before entering...
Ambient gas‐phase and snow‐phase measurements of formaldehyde (HCHO) were conducted at Summit, Greenland, during several summers, in order to understand the role air‐snow exchange on remote tropospheric HCHO factors that determine snowpack HCHO. To investigate impact known emission HCHO, a model was developed includes chemistry relevant Summit is constrained by data from 1999 2000 field campaigns. This gas‐phase‐only does not account for high ambient levels observed previous measurement...
Here we show experimental evidence for the spontaneous chiral resolution of icosahedral [12Pro+H]+ cluster ion. Molecular simulations reveal that icosahedron consists 12 equally spaced prolines where rigid pyrrolidine ring each monomer is sticking out closed cage. The tightly packed cage traps a single proton in center cavity. On other hand, racemic size exhibits prismatic structure can easily incorporate and lose proline monomeric unit sequentially, thus forming geometries. Mechanisms which...
A combination of split-field drift tube/mass spectrometry and isotopic labeling techniques is evaluated as a means identifying single amino acid polymorphisms (SAAPs) in proteins. The method demonstrated using cytochromec (equine bovine) hemoglobin (bovine sheep). For these studies, proteins from different species are digested with trypsin, the peptides labeled at primary amine groups [using either light (H(3))- or heavy (D(3))-isotopic reagent]. SAAP analysis carried out by mixing...
Phenotypic screening provides compounds with very limited target cellular localization data. In order to select the most appropriate identification methods, determining if a compound acts at cell-surface or intracellularly can be valuable. addition, controlling cell-permeability of targeted therapeutics such as antibody-drug conjugates (ADCs) and nanoparticle formulations reduce toxicity from extracellular release drug in undesired tissues direct activity bystander cells. By incorporating...
e24207 Background: Thrombocytopenia is a potential dose-limiting toxicity associated with many oncology agents including BET inhibitors (BETi). in rats closely mirrors clinical thrombocytopenia, enabling the use of this model to explore supportive care options. Methods: A pan-BETi molecule A-1550592 (1mg/kg) was administered by oral gavage for 4 days Sprague Dawley and hematologic parameters measured on Day 5. Recombinant human erythropoietin (rhEPO 150 IU) subcutaneously before...