Unraveling The Molecular Foundations Behind The Diverged Behaviors Of Mouse Insulin 1 And Insulin 2, Connecting Diabetes Risk With Glucocorticoid Treatment And Chronic Migraine Through The Analysis Of Islet Chemistry, And Capturing Key Posttranslational Modifications All Through The Application Of A Novel Lc-Ims-Ms Workflow, 2022 University of Tennessee, Knoxville
Unraveling The Molecular Foundations Behind The Diverged Behaviors Of Mouse Insulin 1 And Insulin 2, Connecting Diabetes Risk With Glucocorticoid Treatment And Chronic Migraine Through The Analysis Of Islet Chemistry, And Capturing Key Posttranslational Modifications All Through The Application Of A Novel Lc-Ims-Ms Workflow, Connor Christopher Long
Select or Award-Winning Individual Scholarship
We display the capabilities of our established liquid chromatography-ion mobility spectrometry-mass spectrometry (LC-IMS-MS) workflow in the investigations of islet chemistry at the sub-single-islet level. We begin by characterizing the structural differences of Ins1 and Ins2 to present novel insights as to why their behaviors diverge. We then examine the effects of the stress hormone corticosterone, the rodent equivalent of human cortisol that is often used as a therapeutic, on pancreatic peptide hormone secretion. We also uncover the molecular connection behind the inverse relationship between type 2 diabetes (T2D) risk and chronic migraine via the neuropeptides CGRP and PACAP. Lastly, we …
The Use Of Hallucinogens In The Treatment Of Mental Health Disorders, 2022 Murray State University
The Use Of Hallucinogens In The Treatment Of Mental Health Disorders, Brianna Gagen
Honors College Theses
The percent of people with mental health disorders in the United States have skyrocketed over the past decade. With stigma surrounding the discussion of mental health and the symptoms associated with it, often those that are suffering do not receive sufficient treatment, as they might with a physical illness. The current, common treatment options for common psychological disorders, like depression, anxiety, and post-traumatic stress disorder, are sometimes not effective in patients, due to resistance or poor response outcomes. Consequently, in order to research alternative therapeutic approaches for mental health disorders, scientists are researching the effects of several hallucinogenic drugs in …
Extraction And Partial Purification Of An Antibiotic-Like Compound From The Soil Bacterium Rhodococcus Strain Kchxc3, 2022 East Tennessee State University
Extraction And Partial Purification Of An Antibiotic-Like Compound From The Soil Bacterium Rhodococcus Strain Kchxc3, Elizabeth Bond
Undergraduate Honors Theses
Rhodococcus bacteria have many secondary metabolic pathways that may produce novel natural products. The bacterium Rhodococcus strain KCHXC3 was isolated from a soil sample collected near Kingsport, Tennessee and was found to produce an inhibitory compound active against a broad array of bacterial species, including the Gram negative pathogen Shigella sonnei. The aim of this research is to extract and purify the compound for future structure elucidation. A mixture of compounds from 3 month old agar plates inoculated with strain KCHXC3 was extracted using ethyl acetate. The crude extract was then partially purified utilizing a Sephadex LH-20 column, followed …
Synthesis Of A Novel Ras Farnesyl Protein Transferase Inhibitor, 2022 St. Cloud State University
Synthesis Of A Novel Ras Farnesyl Protein Transferase Inhibitor, Mark F. Mechelke, Anna Mikolchak
Chemistry Faculty Publications
Mutant RAS proteins are associated with 30% of all human cancers. Unregulated cell growth caused by mutant RAS proteins can be prevented by RAS farnesyl protein transferase (FPTase) inhibitors. A novel FPTase inhibitor has been synthesized incorporating a modified farnesyl “tail” and a customized diphosphate “head”. It is anticipated that the modified “tail”, incorporating a phenyl substituent, will bind more tightly to FPTase due to nonbonding interactions between the aromatic ring and ten aromatic amino acid residues that line the enzyme active site. The altered polar “head”, designed from L-aspartic acid, has already been shown to mimic the natural substrate’s …
An Investigation Towards The Synthesis Of A Novel Conformationally Restricted Ethylenediamine Scaffold, 2022 Montclair State University
An Investigation Towards The Synthesis Of A Novel Conformationally Restricted Ethylenediamine Scaffold, Fanny Mai
Theses, Dissertations and Culminating Projects
This study reports the synthesis of a novel conformationally restricted ethylenediamine scaffold that can be explored for drug discovery. There was significant progress in synthesizing the target scaffolds, but future studies are needed to finish this synthesis. This potential ethylenediamine compound may offer new scaffolds for exploration in drug design and orexin receptor antagonists with improved selectivity for OX1R and OX2R.
The Design Of A Efficient Production And Purification Of Fibroblast Growth Factor 2, 2022 University of Arkansas, Fayetteville
The Design Of A Efficient Production And Purification Of Fibroblast Growth Factor 2, Mandeep Kaur
Chemistry & Biochemistry Undergraduate Honors Theses
Chronic wounds pose a major problem in the United States with an estimate of twenty-five million dollars a year spent on associated treatments. Growth factors can be used as a potential treatment for chronic wounds since they promote cell proliferation and angiogenesis. This study employs one specific growth factor, fibroblast growth factor 2 (FGF2) so that it could potentially be used in future treatment. Wild-type FGF2 is thermally unstable, and it has a mean elimination time of 7.6 hours. This study attempted to improve upon its stability through a mutation on the heparin binding loop. The mutation performed was K134E. …
Bis(Tryptophan) Amphiphiles: Design, Synthesis And Efficacy As Antimicrobial Agents, 2022 University of Missouri-St. Louis
Bis(Tryptophan) Amphiphiles: Design, Synthesis And Efficacy As Antimicrobial Agents, Michael Mckeever
Dissertations
Amphiphiles play important roles in nature. These molecules contain both hydrophilic and hydrophobic regions, leading to some astonishing properties. The lipid bilayer of the cell membrane is a fascinating organization of amphiphilic phospholipids. Natural and synthetic amphiphiles, such as antimicrobial peptides, interact with the cell membrane. Such interactions can impact transport of molecules across the cell membrane, disrupting cell functions. In this work, a library of tryptophan-containing amphiphiles was synthesized and their antimicrobial properties were explored.
First, a library of bis(tryptophan) amphiphiles was synthesized. Preparation included a coupling reaction of a diamine with tryptophan residues, via their carboxy-termini, at …
Synthesis Of Benzophenone-O-Glycosides Under Basic Conditions, 2022 University of Minnesota - Morris
Synthesis Of Benzophenone-O-Glycosides Under Basic Conditions, Samuel Burns
Undergraduate Research Symposium 2022
Type 2 diabetes is a growing health concern worldwide characterized by high blood sugar. Anti-diabetic therapy aims at correcting this sugar imbalance by inhibiting the enzyme α-glucosidase which is responsible for cleaving carbohydrates and starch into glucose. Benzophenone glycosides are a class of biomolecules with α-glucosidase inhibitory properties that have garnered some attention. It can be found and isolated from some traditional medicinal plants which was not done for this project. Once isolated, new derivatives can be synthesized by manipulating protecting groups of the starting material to get the benzophenone. The benzophenone can then undergo glycosylation with the protected sugar …
Fast Photochemical Oxidation And Footprinting Of Proteins Via Trifluoromethyl Radical Chemistry, 2022 University of Mississippi
Fast Photochemical Oxidation And Footprinting Of Proteins Via Trifluoromethyl Radical Chemistry, Elaine Morrow
Honors Theses
Fast photochemical oxidation of proteins (FPOP) is a useful tool in proteomics because of the ability for modifications to occur on the scale of microseconds which reduces the modifications to tertiary and quaternary structure allowing for more accurate labeling of the protein. Labels for FPOP are generated from various radicals in our experiments which include hydroxyl radicals and trifluoromethyl radicals. Hydroxyl radicals are easily generated by using an excimer laser (KrF laser, 248 nm) or a UV flash lamp (as a part of the Fox™ System) by the photolysis of hydrogen peroxide. Trifluoromethyl radicals, however, need hydroxyl radicals to be …
Synthesis And Characterization Of A Novel Reaction-Based Azaborine Fluorescent Probe Capable Of Selectively Detect Carbon Monoxide Based On Palladium-Mediated Carbonylation Chemistry, 2022 Kennesaw State University
Synthesis And Characterization Of A Novel Reaction-Based Azaborine Fluorescent Probe Capable Of Selectively Detect Carbon Monoxide Based On Palladium-Mediated Carbonylation Chemistry, Samuel Moore, Carl Jacky Saint-Louis
Symposium of Student Scholars
Azaborines are fascinating compounds because they possess valuable properties such as photochemical stability, have high molar absorption coefficient and high fluorescent quantum yields, as well as large Stokes shifts and tunable absorption/emission spectra. Here, we designed, synthesized, and will examine a novel reaction-based azaborine fluorescent probe capable of selectively detect carbon monoxide (CO) based on palladium-mediated carbonylation chemistry. This novel azaborine fluorescent probe will exhibit high selectivity for CO and display a robust turn-on fluorescent response in the presence of CO in aqueous buffer solution.
Computer Simulations And Network-Based Profiling Of Binding And Allosteric Interactions Of Sars-Cov-2 Spike Variant Complexes And The Host Receptor: Dissecting The Mechanistic Effects Of The Delta And Omicron Mutations, 2022 Chapman University
Computer Simulations And Network-Based Profiling Of Binding And Allosteric Interactions Of Sars-Cov-2 Spike Variant Complexes And The Host Receptor: Dissecting The Mechanistic Effects Of The Delta And Omicron Mutations, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan
Mathematics, Physics, and Computer Science Faculty Articles and Research
In this study, we combine all-atom MD simulations and comprehensive mutational scanning of S-RBD complexes with the angiotensin-converting enzyme 2 (ACE2) host receptor in the native form as well as the S-RBD Delta and Omicron variants to (a) examine the differences in the dynamic signatures of the S-RBD complexes and (b) identify the critical binding hotspots and sensitivity of the mutational positions. We also examined the differences in allosteric interactions and communications in the S-RBD complexes for the Delta and Omicron variants. Through the perturbation-based scanning of the allosteric propensities of the SARS-CoV-2 S-RBD residues and dynamics-based network centrality and …
Peptidomics Analysis Reveals Changes In Small Urinary Peptides In Patients With Interstitial Cystitis/Bladder Pain Syndrome, 2022 University of Nebraska-Lincoln
Peptidomics Analysis Reveals Changes In Small Urinary Peptides In Patients With Interstitial Cystitis/Bladder Pain Syndrome, Md Shadman Ridwan Abid, Haowen Qiu, Bridget A. Tripp, Aline De Lima Leite, Heidi Roth, Jiri Adamec, Robert Powers, James W. Checco
UNL Student Research Days Posters, Graduate
Interstitial cystitis or bladder pain syndrome (IC/BPS) is a chronic and debilitating pain disorder of the bladder and urinary tract with poorly understood etiology. Symptomatic criteria to aid in the diagnosis of IC/BPS includes bladder pain, an increase in urinary urgency or Hunner’s ulcers on the bladder wall.
Our study revealed differences in the profiles of small urinary peptides for IC/BPS patients compared to age-matched controls which is consistent with increased protease activity in IC/BPS. Our study also enabled the direct measurement of APF peptide abundance in IC/BPS and control urine. Our results indicate that the full-length APF peptide was …
1st Place Contest Entry: Designing Hollow Nanogels For Drug Delivery Applications, 2022 Chapman University
1st Place Contest Entry: Designing Hollow Nanogels For Drug Delivery Applications, Mo Hijazi
Kevin and Tam Ross Undergraduate Research Prize
This is Mo Hijazi's submission for the 2022 Kevin and Tam Ross Undergraduate Research Prize, which won first place. It contains their essay on using library resources, their bibliography, and a summary of their research project on hollow-core nanogels.
Mo is a second-year student at Chapman University, majoring in Biological Sciences. Their faculty mentor is Dr. Molla Islam.
The Development Of Inhibitors For Sars-Cov-2 Orf8, 2022 College of Saint Benedict/Saint John's University
The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen
CSB/SJU Distinguished Thesis
An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be the protein of …
Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, 2022 College of Saint Benedict/Saint John's University
Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen
CSB/SJU Distinguished Thesis
Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has killed an …
Application Of Gellan Gum Biopolymer In Biomedical Applications: A Review, 2022 Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Terengganu 21030, Malaysia
Application Of Gellan Gum Biopolymer In Biomedical Applications: A Review, Norsyakirah Izzati Hishamuddin, Mohd Hasmizam Razali, Khairul Anuar Mat Amin
Makara Journal of Science
Gellan gum (GG) has gained considerable attention in the food, chemical, and pharmaceutical industries due to its functional characteristics. It has versatile properties, such as water solubility, easy bio-fabrication, good film/hydrogel-formation, biodegradability, and biocompatibility. These properties render GG a promising material in biomedical applications, specifically in the development of wound dressing materials. In this review, the use of GG biopolymer as a wound dressing material was discussed. Various fillers, such as titanium dioxides, clay, drug, and honey, have been incorporated in GG to produce film, hydrogel, or scaffold materials. The effects of filler on the mechanical performance, physical properties, antibacterial …
Oxidation Of Thiols To Disulfides Using An Environmentally “Green” Organocatalyst And New Mechanistic Insights, 2022 Old Dominion University
Oxidation Of Thiols To Disulfides Using An Environmentally “Green” Organocatalyst And New Mechanistic Insights, Kosta V. Vlasakakis, Olivia M. White, Robert P. Reynolds, Shayne M. Weierbach, Shannon M. Weaver, Ramsey T. Ritter, Nishi H. Patel, Eric C. Hayes, Sydney Dunmire, Kyle M. Lambert
Undergraduate Research Symposium
The selective oxidation of thiols to disulfides is an area of great importance in the areas of materials and medicinal chemistry research. The production of polymers, rubber, pharmaceuticals, and the folding of proteins in biological systems all rely on the formation of disulfide bonds. Herein, we introduce a stoichiometric and electrocatalytic method for the oxidation of various pharmaceutically and biologically relevant thiols into their respective disulfides in more environmentally benign solvents such as water and alcohol solvents. The scope of the transformation was evaluated and a detailed mechanistic study involving control experiments, experimental kinetic studies, and computational investigations led to …
Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, 2022 Chapman University
Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2. Recent research efforts on the design, protein engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflected a growing realization that nanobody combinations can exploit distinct binding epitopes and leverage the intrinsic plasticity of the conformational landscape for the SARS-CoV-2 S protein to produce efficient neutralizing and mutation resistant characteristics. Structural …
Synthesis And Evaluation Of 11c-Labeled Triazolones As Probes For Imaging Fatty Acid Synthase Expression By Positron Emission Tomography, 2022 Weill Cornell Medicine
Synthesis And Evaluation Of 11c-Labeled Triazolones As Probes For Imaging Fatty Acid Synthase Expression By Positron Emission Tomography, James M. Kelly, Thomas M. Jeitner, Nicole N. Waterhouse, Wenchao Qu, Ethan J. Linstad, Banafshe Samani, Clarence Williams Jr., Anastasia Nikolopoulou, Alejandro Amor-Coarasa, Stephen G. Dimagno, John W. Babich
Chemistry Department: Faculty Publications
Cancer cells require lipids to fulfill energetic, proliferative, and signaling requirements. Even though these cells can take up exogenous fatty acids, the majority exhibit a dependency on de novo fatty acid synthesis. Fatty acid synthase (FASN) is the rate-limiting enzyme in this process. Expression and activity of FASN is elevated in multiple cancers, where it correlates with disease progression and poor prognosis. These observations have sparked interest in developing methods of detecting FASN expression in vivo. One promising approach is the imaging of radiolabeled molecular probes targeting FASN by positron emission tomography (PET). However, although [11C]acetate uptake by …
Chemical Reversible Crosslinking Enables Measurement Of Rna 3d Distances And Alternative Conformations In Cells, 2022 University of Southern California,
Chemical Reversible Crosslinking Enables Measurement Of Rna 3d Distances And Alternative Conformations In Cells, Ryan Van Damme, Kongpan Li, Minjie Zhang, Jianhui Bai, Wilson H. Lee, Joseph D. Yesselman, Zhipeng Lu, Willem A. Velema
Chemistry Department: Faculty Publications
Three-dimensional (3D) structures dictate the functions of RNA molecules in a wide variety of biological processes. However, direct determination of RNA 3D structures in vivo is difficult due to their large sizes, conformational heterogeneity, and dynamics. Here we present a method, Spatial 2′-Hydroxyl Acylation Reversible Crosslinking (SHARC), which uses chemical crosslinkers of defined lengths to measure distances between nucleotides in cellular RNA. Integrating crosslinking, exonuclease (exo) trimming, proximity ligation, and high throughput sequencing, SHARC enables transcriptome-wide tertiary structure contact maps at high accuracy and precision, revealing heterogeneous RNA structures and interactions. SHARC data provide constraints that improves Rosetta-based RNA 3D …