Chemistry Commons^™

Equine In Vivo Metabolite Profiling Of The Selective Androgen Receptor Modulator Lgd-3303 For Doping Control, Malin Nilsson Broberg, Heather Knych, Ulf Bondesson, Curt Pettersson, Börje Tidstedt, Scott Stanley, Mario Thevis, Mikael Hedeland

UK CARES Faculty Publications

LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg⋅kg 1 LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizing ultra-high performance liquid …

Activation Of The Renin–Angiotensin–Aldosterone System Is Attenuated In Hypertensive Compared With Normotensive Pregnancy, Robin C. Shoemaker, Marko Poglitsch, Hong Huang, Katherine Vignes, Aarthi Srinivasan, Cynthia Cockerham-Morris, Aric Schadler, John Anthony Bauer, John O'Brien

UK CARES Faculty Publications

Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin–angiotensin–aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development …

Identification Of Acidic Residues In Proteins By Selective Chemical Labeling And Tandem Mass Spectrometry, Fnu Ashima

Chemistry & Biochemistry Theses - Archive

Proteins play important role in carrying out a wide range of cellular activities. They are subjected to various post-translational modifications (PTMs) by the addition of functional groups such as acetyl, phosphoryl, and methyl which leads to changes in their biological functions, localization, activity, and structure. The growth of MS technology has immensely facilitated the identification of PTMs comprehensively. This dissertation focuses on mapping these changes using covalent labeling techniques by tagging carboxylic acid residues, which undergo various kinds of PTMs. The second chapter focuses on the methods designed for Affinity Purification Mass Spectrometry (AP-MS) chemical cross-linking (CXL) of protein complexes. …

Effects Of Hydrogen/Deuterium Exchange On Protein Stability In Solution And In The Gas Phase, Yousef Haidar, Lars Konermann

Chemistry Publications

Mass spectrometry (MS)-based techniques are widely used for probing protein structure and dynamics in solution. H/D exchange (HDX)-MS is one of the most common approaches in this context. HDX is often considered to be a “benign” labeling method, in that it does not perturb protein behavior in solution. However, several studies have reported that D₂O pushes unfolding equilibria toward the native state. The origin, and even the existence of this protein stabilization remain controversial. Here we conducted thermal unfolding assays in solution to confirm that deuterated proteins in D₂O are more stable, with 2 – 4 …

Enhanced Methods In Forensic Mass Spectrometry For Targeted And Untargeted Drug Analysis, Dina M. Swanson

USF Tampa Graduate Theses and Dissertations

Forensic science has long used mass spectrometry for the analysis of drugsand metabolites. Traditionally, screening methods consisted of color tests or immunoassay and confirmation methods used gas chromatography with mass spectrometry, which was considered the gold standard for identification. In the last several decades, advances in liquid chromatography with mass spectrometry (LCMS) have brought this technology to the forefront of forensic drug identification. Drug identification in forensic drug chemistry and forensic toxicology has become increasingly challenging due to the rapid increase in illicit drug analogs including novel opioids such as fentanyl analogs. Traditional screening methodologies are often unable to identify …

Epimeric Peptides In Alzheimer’S Disease: Implications For Liquid Chromatography-Mass Spectrometry And Immunotherapies, Elizabeth Readel

Chemistry & Biochemistry Dissertations - Archive

Evidence has shown that the extracellular deposition of amyloid-beta (Aβ) peptide is a contributing factor of Alzheimer’s disease. Further, modifications to Aβ peptides may enhance the deposition of Aβ plaques and/or contribute to the neurodegeneration in AD patients. These aberrations include the isomerization and epimerization of L-Asp and D-Ser residues to form D-Asp, L/D-iso-Asp, and D-Ser residues, respectively. Therefore, considerable effort has been expended to create effective methods to distinguish such aberrant Aβ peptides from wild type. A useful technique to extract aberrant Aβ peptides in AD patients is by immunotherapies, or antibodies. A few immunotherapies are thought to provide …

Developing Chemo-Proteomics Methods For Tyrosine Conjugation And Studies Of Organometallic Complexes Of Gold., Adway Ouseph Zacharias

Chemistry & Biochemistry Dissertations - Archive

The incredible changes in MS instrumentation since the late 1980s with the advent of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) has revolutionized protein chemistry. Mass spectrometry coupled with chemical crosslinking is a powerful tool to decipher protein structure and protein-protein interactions. A majority of commercially available crosslinkers target only few amino acid residues such as lysine, arginine and cysteine, thereby limiting the utility of this technology. The prospect of using chemical reagents to target amino acids is challenging since covalent labeling experiments are performed under physiological aqueous conditions that may be detrimental to the stability of these reagents. …

Quantitative Analysis Of The Proteomic Selectivity Of Acidic Reductive Alkylation Of Peptides, Connor Jewell

Honors Scholar Theses

Proteome quantification is a complicated process which takes on many methods, usually involving peptide derivatization and complex mass spectral analysis. Scores of techniques have been utilized to address issues of incomplete quantification. The implementation of IPTL labeling, or isobaric peptide terminal labeling, is a recent addition to the literature, which exploits the supposedly selective labeling of N-termini of tryptic peptides from the C-termini of lysine residues due to differences in basicity. This method has been shown to improve quantitation by reducing spectral complexity and provide more accurate and reproducible results on peptide abundance. Investigations into the selectivity of terminal derivatization …

Development And Validation Of A Liquid Chromatography-Tandem Mass Spectrometry Method For The Determination Of Temozolomide In Mouse Brain Tissue, Raghavi Kakarla, Kimberly Yacoub, Rebecca L. Bearden, Aimin Zhou, Sanjib Mukherjee, Frank Y. Shan, Baochuan Guo

Chemistry Faculty Publications

Temozolomide is a Food and Drug Administration-approved anticancer drug that has poor drug delivery via oral or intravenous routes. A potential strategy to combat this problem is investigating alternative routes of administration, requiring quantitation of the drug in the brain tissues by liquid chromatography-mass spectrometry. However, current methods used to extract the drug from brain tissues resulted in poor recovery and substantial matrix effects. Herein, we reported a new two-step extraction method that involves the use of Proteinase K to lyse tumor tissues to efficiently release the drug, followed by ethanol protein precipitation. The extracts were then separated on a …

Tenvr: Matlab-Based Toolbox For Environmental Research, Aleksandar I. Goranov, Rachel L. Sleighter, Dobromir A. Yordanov, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

With the advancements in science and technology, datasets become larger and more multivariate, which warrants the need for programming tools for fast data processing and multivariate statistical analysis. Here, the MATLAB-based Toolbox for Environmental Research "TEnvR" (pronounced "ten-ver") is introduced. This novel toolbox includes 44 open-source codes for automated data analysis from a multitude of techniques, such as ultraviolet-visible, fluorescence, and nuclear magnetic resonance spectroscopies, as well as from ultrahigh resolution mass spectrometry. Provided are codes for processing data (e.g., spectral corrections, formula assignment), visualization of figures, calculation of metrics, multivariate statistics, and automated work-up of large datasets. TEnvR allows …

Development Of New Mass Spectrometric Approaches For Biomarker Discovery: Application To Complex Biological Matrices For Tissue Characterization And Disease Diagnosis, Allix Marie Coon

Legacy Theses & Dissertations (2009 - 2024)

In this work, the newly developed technique laser ablation direct analysis in real – time high-resolution imaging mass spectrometry (LADI-MS) and the more established methods direct analysis in real time – high-resolution mass spectrometry (DART-HRMS) and two-dimensional gas chromatography – mass spectrometry (GC×GC-MS), were used to interrogate challenging plant- and human-derived complex matrices that have proven difficult to analyze by conventional methods, in order to extract heretofore inaccessible information that can be applied to the understanding of wood systems biology, ecophysiology, dendrochronology and natural product isolation of biologically relevant compounds (on the plant side), and explore the potential for discovery …

Developing Novel Femtosecond Time-Resolved Mass Spectrometry Techniques For Analysis Of Energetic Materials, Shane L. Mcpherson

Theses and Dissertations

Energetic materials and the unimolecular dissociation dynamics attributed to their initiation and subsequent bimolecular detonation have been a subject of interest for defense agencies such as the Department of Defense (DoD) for decades. The timescale in which these initial dynamics exist ranges from several picoseconds to dozens of femtoseconds, necessitating equally fast time-resolved experiments to capture and characterize these events. Our lab specializes in one such laser-based technique: femtosecond time-resolved mass spectrometry (FTRMS). FTRMS is an essentially nondiscriminatory pump-probe laser technique with nearly infinite modifications via pulse shaping, intensity, and wavelength modulation that can readily examine previously undefined dissociation pathways …

Investigation Of Early Complex Formation Of Huntingtin Protein With And Without Lipids, Alyssa R. Stonebraker

Graduate Theses, Dissertations, and Problem Reports (ETD)

Huntington’s disease (HD) is a fatal neurodegenerative disease caused by the expansion of the polyglutamine (polyQ) domain of the huntingtin protein (htt). The expansion of the polyQ domain beyond a threshold of approximately 35 repeats triggers complex toxic aggregation mechanisms and results in altered interactions between htt and lipid membranes. Many factors modulate these processes. One such modulator includes sequences flanking the polyQ domain, most notably the first 17 amino acids at the N-terminus of the protein (Nt17), and environmental factors including the presence of membranous structures. Nt17 has the propensity to form an amphipathic a-helix in the presence of …

The Influence Of Instrumental Sources Of Variance On Mass Spectral Comparison Algorithms, Isabel Cristina Galvez Valencia

Graduate Theses, Dissertations, and Problem Reports (ETD)

Current search algorithms for the identification of substances based only on their electron ionization mass spectra provide the correct compound as their top result approximately 80% of the time. One contributing factor to the ~20% deviation in the first-hit recognition rate is that traditional algorithms work by comparing the unknown spectrum to an ‘ideal’ or consensus spectrum of each reference compound. The inclusion of replicate reference spectra in a database has been shown to improve the probability of ranking the correct identity in the number one position, but the variance in ion abundances caused by different conditions or different instruments …

Application Of Mass Spectrometry For The Characterization Of Synthetic Oligomers And Natural Lignin, Poorya Kamali

Theses and Dissertations--Chemistry

As part of the ongoing effort to substitute finite fuel and chemical resources with renewable ones, biomass is emerging as one of the most promising sources. Biomass consists of three main components of cellulose, hemicellulose, and lignin. Traditionally, cellulose has been used extensively in pulping industry, while lignin has been considered waste and is burned to generate heat. Lignin, a complex aromatic polymer component of biomass, has the potential to be used as a source of aromatic chemicals and pharmaceutical synthons. The recalcitrant nature of lignin, the lack of effective lignin breakdown methods and analytical techniques to analyze it are …

Investigating The Dynamics And Fragmentation Of Nitroaromatic Radical Cations Through Femtosecond Time-Resolved Mass Spectrometry And Computational Chemistry, Hugo Andres Lopez Pena

Theses and Dissertations

Chemists have sought to control molecular dissociation with lasers for decades. Effective control of unimolecular dissociation was only achieved with the development of high-intensity ultrashort pulsed lasers and coherent control techniques that operate on timescales faster than vibrational energy redistribution. In view of this, our lab has specialized in the study of polyatomic radical cations using femtosecond time-resolved mass spectrometry (FTRMS). The interest in radical cations stems from the fact that they are highly reactive species that contribute to many physical, chemical, and biological processes. For instance, radical cations participate in shock initiation of detonated energetic materials used as explosives …

Polyphenols And Small Phenolic Acids As Cellular Metabolic Regulators, Mark Obrenovich, Yi Li, Moncef Tayahi, V. Prakash Reddy

Chemistry Faculty Research & Creative Works

Polyphenols and representative small phenolic acids and molecules derived from larger constituents are dietary antioxidants from fruits, vegetables and largely other plant-based sources that have ability to scavenge free radicals. What is often neglected in polyphenol metabolism is bioavailability and the role of the gut microbiota (GMB), which has an essential role in health and disease and participates in co-metabolism with the host. The composition of the gut microbiota is in constant flux and is modified by multiple intrinsic and extrinsic factors, including antibiotics. Dietary or other factors are key modulators of the host gut milieu. In this review, we …

Meta-Analysis Reveals Both The Promises And The Challenges Of Clinical Metabolomics, Heidi E. Roth, Robert Powers

Department of Chemistry: Faculty Publications

Clinical metabolomics is a rapidly expanding field focused on identifying molecular biomarkers to aid in the efficient diagnosis and treatment of human diseases. Variations in study design, metabolomics methodologies, and investigator protocols raise serious concerns about the accuracy and reproducibility of these potential biomarkers. The explosive growth of the field has led to the recent availability of numerous replicate clinical studies, which permits an evaluation of the consistency of biomarkers identified across multiple metabolomics projects. Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death and has the lowest five-year survival rate primarily due to the lack of an …

Quantifying Protein Quality To Understand Protein Homeostasis (Supplemental Data), Hsien-Jung Lavender Lin

ScholarsArchive Data

This data set includes the supplementary data for chpaters 3 and 4 in the dissertation Quantifying Protein Quality to Understand Protein Homeostasis. It includes various excel worksheets that were used to generate the data reported in the dissertation. We make this data available to the public so anyone who wants to reproduce the results has the resources and access to other perspectives that weren't discussed in depth in the dissertation. Chapter 3 used mass-spectrometry to quantify the surface accessibility differences in human serum albumin (HSA)between patients with and without rheumatoid arthritis (RA). We found certain residues are less reactive …

Analysis Of The Zebrafish Olfactory System Using Immunohistochemistry And Enhanced Techniques Of Desorption Electrospray Ionization Mass Spectrometry (Desi-Ms), Tara Lynn Maser

Dissertations

Desorption electrospray ionization (DESI-MS) is an ambient ionization technique where the sample is analyzed directly from a surface with very minimal sample preparation under ambient conditions and follows ESI-like ionization mechanisms. DESI-MS has proven powerful in analyzing or imaging lipids and other small molecules directly from biological samples and even allows for subsequent histological staining and analyses. However, DESI-MS is less widely used for protein analysis due to a lack of sensitivity and the complex diversity of proteins in biological samples.

A major goal of this research has been to obtain new neurobiological knowledge by combining histology and mass spectrometry …

Atmospheric Mercury Chemistry: Detection, Kinetics, And Mechanism, Na Mao

Dissertations

The presence of mercury in the environment is of global concern due to its toxicity. The atmosphere is an important transient reservoir for mercury released by human activities and natural sources. The knowledge of atmospheric mercury chemistry is critical for understanding the global biogeochemical cycle. In the atmosphere, mercury primarily exists in three forms: gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM), and particulate-bound mercury (PBM). Over the last decade, the existing knowledge of mercury cycle has dramatically changed: (1) There has been increasing evidence that current detection methods do not accurately quantify gaseous oxidized mercury and a technique which …

Development Of Novel Mass Spectrometric Methods For Reaction Screening, Oligosaccharide Detection, And Nitrosamine Quantitation, Qi Wang

Dissertations

Benefitting from its high detection sensitivity and specificity, mass spectrometry (MS) has become a powerful technique in academia and industry. The aim of this dissertation study is to develop new mass spectrometric methods for organic reaction screening, detection of oligosaccharide/glycan in complex matrices, and nitrosamine absolute quantitation.

First, an electrochemistry/mass spectrometry (EC/MS) platform is built to generate an N-cyclopropylaniline radical cation electrochemically and to monitor its reactivity toward alkenes, which leads to the discovery of a new redox neutral reaction of intermolecular [3 + 2] annulation of N-cyclopropylanilines and alkenes. Net redox neutral electrosynthesis is quite rare in synthetic organic …

Investigation Of The Analytical Utility Of The Inductively Coupled Plasma Mass Spectrometer (Icp-Ms) For The Quantification Of Proteins Via Lanthanide Labeling, Caitlin Elizabeth Dunlap

Undergraduate Honors Thesis Collection

The discovery and ability to provide an absolute concentration of biomarkers in the body can facilitate early diagnoses of diseases. This information can also be used for more accurate and unique treatments for those patients. While major advances in molecular mass spectrometry allows for a sensitive identification of these biomarkers, they are limited to only four orders of magnitude in their dynamic ranges. Due to this, detection and quantitation of low abundant proteins, which tend to make up these vital biomarkers, is very difficult. On the other hand, ICP-MS offers a wider dynamic range (up to 12 orders of magnitude) …

Microbial Labilization And Diversification Of Pyrogenic Dissolved Organic Matter, Aleksandar I. Goranov, Andrew S. Wozniak, Kyle W. Bostick, Andrew R. Zimmerman, Siddhartha Mitra, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

With the increased occurrence of wildfires around the world, interest in the chemistry of pyrogenic organic matter (pyOM) and its fate in the environment has increased. Upon leaching from soils by rain events, significant amounts of dissolved pyOM (pyDOM) enter the aquatic environment and interact with microbial communities that are essential for cycling organic matter within the different biogeochemical cycles. To evaluate the biodegradability of pyDOM, aqueous extracts of laboratory-produced biochars were incubated with soil microbes, and the molecular changes to the composition of pyDOM were probed using ultrahigh-resolution mass spectrometry (Fourier transform–ion cyclotron resonance–mass spectrometry). Given that solar irradiation …

Marcadores Moleculares Subrogados A La Repelencia Al Agua En Suelos Afectados Por El Fuego, Nicasio T. Jiménez-Morillo, Gonzalo Almendros, Nuno Guiomar, Ana Z. Miller, Cristina Barrocas-Dias, José M. De La Rosa, Patrick G. Hatcher, José A. González-Pérez

Chemistry & Biochemistry Faculty Publications

Soil water repellency (SWR) is often attributed to the accumulation of hydrophobic organic compounds, mainly lipids. Nonetheless, lipid extraction not always suppress SWR and unextractable soil constituents may be related with residual SWR. Burnt (B) and unburnt (UB) soils (Doñana National Park, Huelva) under two vegetations (cork oak and heather) and two soil fractions, coarse (1–2 mm) and fine (

Uio-Type Metal-Organic Framework Derivatives As Sorbents For The Detection Of Gas-Phase Explosives, Matthew Ryan Sherrill

Legacy Theses & Dissertations (2009 - 2024)

The detection of energetic compounds – better known to the public as explosives – has is an important cornerstone of counterterrorism and homeland security . While significant advances have been achieved for the detection of trace explosives in various matrices such as soil, wastewater, and clothing, the detection of explosives in the gas phase remains challenging due to their infamously low vapor pressures. In this thesis, we leverage the high sensitivity of direct analysis in real-time mass spectrometry (DART-MS) and the microporosity of metal-organic frameworks (MOFs) to adsorb and therefore concentrate explosives from the vapor phase and subsequently detect them …

Development And Applications Of Touch Chemistry Biometrics Analysis Of Latent Fingermarks By Maldi-Ms, Cameron M. Longo

Legacy Theses & Dissertations (2009 - 2024)

Fingerprint evidence has long been a pillar of forensic science and has been used for over a century as a means of identifying an individual. This is accomplished through the comparison of friction ridge patterns, which are inherently unique to each individual, and the practice of visualizing fingerprints and comparing them has become a well-studied field. While these techniques have been optimized and improved over time, they generally rely only on the physical pattern to provide information about the donor, and not the content of the fingerprint material itself. In the modern era, steps have been made to extract from …

Electrochemical And Mass Spectrometry Methods For Identification Of Gunshot Residues (Gsr) In Forensic Investigations, Kourtney A. Dalzell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Gun violence continues to be one of most significant challenges straining the USA society causing thousands of human lives lost every year. In 2020 alone, firearm-related incidents including homicide, accidents, and suicides, reached a staggering number of over 43,000.^1,2 With the increase in these types of incidents, several service areas in crime laboratories are heavily impacted by the number of cases run on a yearly basis. These include firearm examinations, gunshot residue (GSR) analysis, bullet hole identification, and shooting distance determination, which are crucial to support a criminal investigation and, overall, the justice system in our country. These areas …

Analysis Of Forensically Relevant Evidence Using Electrochemistry, Spectroscopy, And Mass Spectrometry Tools, Colby Edward Ott

Graduate Theses, Dissertations, and Problem Reports (ETD)

Forensic science relies on the use of multiple techniques in the assessment of evidence to increase the accuracy and reliability of the results. However, with the rapidly changing drug landscape due to the introduction of novel psychoactive substances, many traditional screening methods are no longer sensitive or selective enough for use. Additionally, many screening methods such as chemical color tests are prone to false positive and negative results and are subjective. Therefore, the goal of this dissertation was to develop a novel analytical scheme that can provide a more efficient, rapid, and sensitive method that will facilitate adoption in the …

Capillary Electrophoresis: Method Development And Application In Biomolecule Analysis, Lindsay Marie Veltri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Abstract

Capillary Electrophoresis: Method Development and Application in Biomolecule Analysis

Lindsay Veltri

Biomolecule analysis is essential in disease diagnostics and the development of therapeutic agents. There is a vast array of methods available for biomolecule analysis, however, capillary electrophoresis is well-suited due to minimal sample consumption (~nanoliters of solution) and fast analysis times. In this report, capillary electrophoresis was used to analyze glycosylation of therapeutic proteins. Additionally, a capillary electrophoresis-mass spectrometry method is reported for the analysis of proteins.

Post-translation protein modifications like glycosylation, play an important in protein structure and function. Modifications of protein glycosylation can lead to improved …