Chemicals and Drugs Commons^™

Cortisol Receptor Sensitivity As A Risk Factor For Depression, Michela Michielli

Honors Theses

In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic-Anterior-Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).

Our research has examined mutations known as single-nucleotide-polymorphisms (SNPs) relating to cortisol-receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and …

Diisopinocampheylborane Trifluoromethanesulfonate-Mediated Aldol Reactions Using An Aldehyde And An Amide, Camille Parker

Honors Theses

Aldol reactions are one of the most powerful reactions in organic chemistry because of the formation of new carbon-carbon bonds. A downside of aldol reactions is that they generate a mix of stereoisomers, therefore a lot of work has gone into developing methods that selectively favor a certain stereoisomer. We report an enatio and diastereoselective diisopinocampheylborane trifluoromethanesulfonate ((Ipc)₂BOTf) mediated aldol reaction with an amide and an aldehyde. Traditionally, (Ipc)₂BOTf-mediated reactions were not applied to amides, except with the use of strong bases. Here we developed a (Ipc)₂BOTf aldol reaction of amides using mild bases …

Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell

Honors Theses

One of the main causes of neurodegenerative diseases is aggregation of amyloid proteins that are toxic to the neurons. Proteins like amyloid-β (Aβ) and α-syneuclein (α-syn) form hallmark aggregate lesions that contribute to pathological processes in the brain in Alzheimer and Parkinson’s patients, respectively. Recent ground-breaking studies have suggested a link between the microbiota of the gut and neurodegenerative diseases, called the “gut-brain axis.” It has been long known that the protein, CsgA found in many enteric bacteria, forms amyloid fibers of its own called Curli. Curli fibrils are a structural component of bacterial colonies and maintain the integrity of …

A Study Of Dextran As A Macromolecular Crowding Agent, Katherine Morgan

Honors Theses

Deoxyribonucleic acid (DNA) is the hereditary material in all living organisms. According to the Watson and Crick model, DNA exists as two long strands coiled into a double helix. However, DNA has been found to have the potential to exist in secondary forms known as G-Quadruplexes and i-motifs. I-motifs (intercalated-motif or iM) are formed under acidic conditions when sets of cytosines pair with protonated cytosines and are looped around each other. The pKa value for iMs in dilute solutions is approximately 6.5, but iMs can potentially exist at a higher, physiological pH value under crowded conditions. Within the interior of …

The Synthesis And Characterization Of Ionic Liquids Using Nitrogen-Based Cations For Transdermal Delivery, Jo Galloway

Honors Theses

The purpose of this research was to explore the synthesis mechanisms of water-soluble ionic liquids with nitrogen-containing cationic bases for future use in transdermal drug delivery and forensic science applications. Ionic liquids are salts with an organic cation and either an organic or inorganic anion. They have asymmetric structures, which means that the molecules don’t pack together as neatly as other salts do, therefore, they don’t crystallize as easily, and their melting points are lower. Ionic liquids have melting points below 100°C, and many are liquid at room temperature. Mechanistic studies reveal that the potency of ILs in enhancing transdermal …

The Effects Of Thc On Hiv Tat Protein-Mediated Neuroinflammation, Camille Martin

Honors Theses

Although antiretroviral therapies have allowed people living with human immunodeficiency virus (HIV) to achieve normal life expectancies, they cannot cure HIV nor the neurological symptoms associated with infection, termed neuroHIV. NeuroHIV describes a myriad of neurological disorders including mood disorders (depression and anxiety), cognitive impairment, neuropathic pain, and motor disinhibition. The mechanisms by which HIV promotes neurological impairment are not known, but may involve actions of its neurotoxic proteins. One such protein that has been well-characterized is the HIV trans-activator of transcription (Tat). Tat exerts neurotoxic effects via various means, one of which is to activate microglia, the macrophages of …

Lectin-Glycan Complexes: A Comprehensive Analysis Of Docking Calculations, Ashton Custer

Honors Theses

Lectins are a type of glycan-binding protein that noncovalently bind glycans. Carbohydrates are molecules consisting of sugar units joined together. Glycans are carbohydrates. Hence, glycans are also sugars. Lectins and lectin-glycan complexes have a range of biological roles and can be found in animals (including humans), plants, bacteria, viruses, and yeasts and fungi.¹ Many scientists focus on the computational study of these complexes due to their intricate roles in many living organisms. Computational study is important in furthering our knowledge of lectin-glycan complexes and other such protein complexes. However, computational study is not perfect. There are many challenges in …

Lc-Ms Identification Of Serum Proteins Adsorbed Onto Ionic Liquid-Coated Nanoparticles, Anh M. Hoang

Honors Theses

Nanocarriers are promising candidates for drug delivery due to their size and tunable surface characteristics. However, when they are intravenously injected, few particles make it to their designated location. This is because upon entering the bloodstream, the serum in the blood, which is rich with a diversity of proteins, adsorbs onto the particles’ surfaces forming a protein corona. Many of the attached proteins trigger the mobile immune system and are removed by macrophages, and many particles are then filtered out by the liver and kidneys. Ionic Liquids (ILs), which consist of asymmetric, bulky components that are liquid

Synthetic Investigations In Chemical Probe Development Part 1: Design And Synthesis Of Novel Triton X-405 Adenosine Conjugates; Part 2: Synthesis Of 2,8-Dihydroxychrysene, Rachel Irene Hammond

Honors Theses

Although not drugs themselves, chemical probes are a necessary tool in biomedical research for the interrogation of biological systems. In the present synthetic investigation, two chemical probes were developed – a Triton X-405 adenosine conjugate (TX-405A) and 2,8-dihydroxychrysene. The designed TX-405A conjugate was generated in four steps through tosylation and amination of TX-405 such that EDC-coupling of TX-amine with 2’,3’-Isopropylidene adenosine-5’-carboxylic acid afforded TX-405A following acetonide deprotection. The development of TX-405A represents the first report of the synthesis and utilization of a detergent-linked dosimeter. The synthesis of 2,8-dihydroxychrysene provided an in-depth exploration on the unique reactivity of chrysene. The desired …

Effects Of Waterborne Benzo[A]Pyrene Embryonic Exposure On Development, Behavior, Reproduction, And Mitochondrial Bioenergetics In Zebrafish, Megha Patel

Honors Theses

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is a known carcinogen leading to adverse effects in the development of both humans and animals. BaP is also continuously present in the environment leading to regular exposure via inhalation or ingestion. Because organisms’ early life stages can be more susceptible to contaminant exposure, our focus was on BaP’s adverse impacts on survival, length, weight, behavior, bioenergetic state, and fecundity following developmental exposures. To study BaP’s impacts, zebrafish (Danio rerio) were used as a model organism. BaP is a ligand for the aryl hydrocarbon receptor (AHR in humans; Ahr in …

The Role Of Age Ligand And Rap1a In Myofibroblast Signaling Cascade In Type 2 Diabetes Mellitus-Induced Cardiomyopathic Conditions, Camilla Puglia

Honors Theses

Diabetes is one of the leading causes of death in the United States, taking more than 90,000 lives annually. Type 2 diabetes mellitus-induced cardiac fibrosis is a common condition seen in diabetic patients. The AGE/RAGE signaling cascade has been strongly associated with this supposed cardiac fibrosis along with hyperactive myofibroblasts which excessively remodel extracellular matrix tissue, leading to damaged and enlarged heart muscle tissue. In diabetic patients, Advanced Glycation End Products (AGEs) are produced in abundance and accumulate in the extracellular matrix of heart tissue. To investigate the role of of the AGE ligand on fibroblast behavior, increasing amounts of …

Investigation Into The Detection Of Drug Metabolites In Latent Fingerprints, Paige Oden

Honors Theses

Fingerprinting has proved a useful mode of identification for thousands of years. Following numerous technological advancements, it has become a technique for categorizing and keeping track of people over large geographical spaces for almost half of a century. Those living in the beginnings of fingerprinting used them as a form of signature as it was something completely unique to each individual that could not be replicated. Although they are no longer used as the primary form of signature, it certainly remains a biomarker of identity. Over the past century the practice has been heavily refined in order to identify people …

Characterizing The Roles Of Cannabinoid Receptor 1 & 2 In Zebrafish Behavior, Metabolism, And Seizure-Induced Activity, Kayci Kimmons

Honors Theses

Epileptic disorders like Dravet Syndrome require novel studies to determine the most ideal treatment. New research linking the endocannabinoid system (ECS) to epileptic disorders is arising, but there is still much to be discovered about the function and regulatory impact of the endocannabinoid system and its receptors in epilepsies like Dravet. In this study, knockout models of larval and adult zebrafish (Danio rerio) were used to investigate the roles of cannabinoid receptors 1 & 2 in behavior, brain mitochondrial metabolism, and seizure-induced activity following exposure to THC and CBD. Larval zebrafish which lacked cannabinoid receptor 1 exhibited increased …

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu

Honors Theses

RAS is a prevalent oncogene that is mutated in 27% of human cancers. Gain-of-function RAS mutations activate multiple downstream pathways, including the RAS-RAF-MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. RAS proteins such as KRAS, a member of the RAS protein family, and their downstream effectors are attractive targets for cancer therapy since their mutations act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named MCI-062 was …

Targeting Platelets Using Ionic Liquid Coated Nanoparticles, Karen Mun Wong

Honors Theses

Platelets are key players in our body’s inflammatory processes upon activation, which can create physiological problems. Researchers are actively seeking solutions by targeting platelets with therapeutics. The objective of the research in this thesis was to investigate a new and potentially less invasive drug delivery platform using nanoparticles. The topic of the project was to explore the world of ionic liquids and their abilities, when coated on nanoparticles, to bind to platelets. A library of choline carboxylic acid-based ionic liquids (ILs) was first synthesized via salt metathesis while PLGA-based nanoparticles were simultaneously being synthesized via the nanoprecipitation method. The ionic …

"It’S Just Another Thing”: Perceptions Of Well Water Quality And Barriers In An Arsenic Hot Spot, Linzy Rosen

Honors Theses

Privately owned water is the primary source of drinking water for 43 million Americans. Although residential or private wells are susceptible to a variety of contaminants, the Safe Drinking Water Act of 1974 positions individuals as responsible for the testing, remediation, and management of this water. Despite the elevated presence of arsenic in Maine, which is linked to various cancers, cardiovascular disease, and neurological damage, little is known about how private well owners perceive the safety and quality of their own water.

This study takes a qualitative approach to understanding concerns and opinions by conducting semi - structured interviews with …