Biochemistry Commons^™

Increased Backbone Rigidity Of Artificial Transcription Factors, Jasmine Glover, Emma Otey, Joanna K. Kwao, Nicholas Truex

Senior Theses

Programming DNA-binding proteins is an effective strategy for developing therapeutics that regulate gene expression. These proteins can directly bind to DNA to activate or repress transcription of specific genes. Zinc finger proteins are a class of DNA-binding proteins commonly found in eukaryotic organisms. Their DNA-binding function is derived from unique amino acid sequences within each domain that recognizes specific nucleotides, allowing each finger to selectively recognize three DNA base pairs. Adjoining of multiple domains in tandem allows recognition of a specific DNA sequence. Artificial transcription factors can be made of multiple zinc finger domains arranged in tandem and engineered to …

Lighting Up The Cell: Developing A Luminescent Lanthanide Probe For Detecting Rnas, Jonathan Savell

Honors Projects

An anion detecting luminescent probe, Tb:DO2A-Cs124, was repurposed for use in RNA imaging. Potential RNA aptamers were identified for the molecule using Capture-SELEX and MinION sequencing. Fluorimetry data revealed these aptamers did not allow for the probe to luminesce in the presence of target RNAs due to adenosine monophosphate’s ability to quench the emission signal.

Phosphomimetic Substitution Of Serine Residue Ser260 With Aspartate Suggests Regulation Of Activity Of Human Cytosolic Malate Dehydrogenase By Phosphorylation, Charles Pelagalli '25, Luke Tischio, Kathleen Cornely

Chemistry & Biochemistry Faculty Publications

Human cytosolic malate dehydrogenase (MDH1) is a key enzyme involved in the malate-aspartate shuttle of eukaryotic cells, and which catalyzes the reaction of oxaloacetate to malate. As MDH1 is responsible for maintaining redox homeostasis by regeneration of NAD+ for glycolysis, its regulation is of particular interest in pharmaceutical applications, specifically in treating cancer cells that proliferate quickly and hence rely greatly on glycolysis. While the regulation of MDH1 by the phosphorylation of key residues has been previously documented, work still remains in identifying the specific residues involved in regulation of the enzyme by phosphorylation. In this study, we used …

Exploring The Role Of Azoreductase Enzymes In Drug Metabolism: Implications For Personalized Medicine, Najoude Claude, Robert Ghergurovich

Chemistry & Biochemistry Student Scholarship

Najoude Claude ’26, Biology major

Robert Ghergurovich ’26, Biochemistry major

Faculty mentor: Dr. Tyler Stack, Chemistry and Biochemistry

The gut microbiome hosts trillions of microorganisms that metabolize xenobiotics such as drugs and food dyes. Individual differences lead to variable drug metabolism. We studied two azoreductases: E. coli’s P41407 and Alistipes sp. CHKCL003’s A0A143XFE8. Enzyme P41407 acted on methyl red and ethyl red, while A0A143XFE8 acted on these and also on phenol blue, HMND, and sunset yellow. We propose these enzymes function as quinone reductases, requiring a quinone-like intermediate. Three synthesized compounds confirmed similar kinetics. In conclusion, these insights significantly advance …

Discovery, Purification And Annotation Of Four Novel Mycobacteriophages In New England, Mason Krawczynski

Chemistry & Biochemistry Student Scholarship

Mason Krawczynski ’26, Biology and Psychology major

Faculty mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Mycobacteriophages are viruses that infect bacteria of the Mycobacterium genus. Several thousand mycobacteriophages have been discovered, isolated, and characterized to advance the current understanding of their genomic diversity. The mycobacterium phage selection proves valuable, as they have a broad host range and potential for therapeutic application to treat pathogenic and antibiotic-resistant mycobacteria, such as Mycobacterium tuberculosis, the causative agent of tuberculosis infection. Kraw was isolated from a soil sample collected in Oaks Bluff, Massachusetts, on the island of Martha’s Vineyard in July 2023. FairyPath, Calvinny, …

Tools For Harnessing Atropisomerism In 1-Aryl-Β-Carbolines, Cristina Díaz, Malaquias Loiza, Josef Crenshaw, Brian Ladino, Elizabeth Perda, Alma Martinez, Joseph Mazzucca, John Stathoulopoulos

Chemistry & Biochemistry Student Scholarship

Cristina Díaz ’25, Chemistry major

Malaquias Loiza ’26, Biochemistry major

Josef Crenshaw ’28, Biochemistry major

Brian Ladino ’28, Biochemistry major

Elizabeth Perda ’26, Biochemistry major

Alma Martinez ’26, Biochemistry major

Joseph Mazzucca ’25, Biochemistry major

John Stathoulopoulos ’26, Chemistry major

Faculty mentor: Dr. Seann Mulcahy, Chemistry and Biochemistry

Axially chiral molecules with high barriers to rotation are becoming increasingly more prominent in drug discovery, chemical biology, and materials science. We have shown that 1-aryl-β-carbolines exhibit high configurationally stability, with barriers to rotation greater than 30 kcal/mol and have recently disclosed an asymmetric synthesis of these molecules. In this presentation, we …

Discovery, Purification And Annotation Of A Novel Mycobacteriophage Discovered On The Providence College Campus, Jenna Greene

Chemistry & Biochemistry Student Scholarship

Jenna Greene ’26, Biochemistry major

Faculty mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Bacteriophages—viruses that infect bacteria—offer a promising alternative to antibiotics in the face of rising antibiotic resistance. In this project, I isolated a novel phage from a soil sample collected in front of Raymond Dining Hall at Providence College. Using Mycobacterium smegmatis as the host, the sample underwent multiple rounds of purification until a single phage, named GMonster (a nod to my family nickname, “Greene Monster”), was isolated. GMonster was submitted to the PhagesDB database and confirmed through sequencing to belong to the A1 cluster—the first of its …

Exploring An Electron-Rich Iron Tricarbonyl Complex Containing An Α-Diimine Ligand, Joseph Maher

Chemistry & Biochemistry Student Scholarship

Joseph Maher ’25, Chemistry major

Faculty mentor: Dr. Maria Carroll, Chemistry and Biochemistry

The combustion of fossil fuels increases atmospheric CO2, making hydrogen a promising cleaner energy alternative. Pt has been able to facilitate this reaction efficiently, however, it is expensive and scarce. Fe has shown promise in facilitating 2-electron transfers when bound to redox-active ligands. Reacting the redox-active CyDABMe with benzylidene acetone iron tricarbonyl (bdaFe(CO)3) forms Fe[CyDABMe](CO)3, with vCO values ~10 cm-1 lower than FeArDABMe(CO)3, indicating increased electron density. The reduction potential of CyDABMe was probed using Zn[CyDABMe]Cl2, showing a reduction at 200 mV more negative than Zn[ArDABMe]Cl2. X-ray …

Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill

Open Educational Resources

A wonderful blend of physiology, nutrition, biochemistry, genetics, biology, evolution, chemistry--what we all need to know as informed citizens. A basic knowledge of the life sciences and how our bodies work--to promote our own good health, especially as we're bombarded with misleading advertisements, soundbites, and the like. DNA fingerprinting, calorie requirements, dietary advice, genetic engineering (including gene editing with CRISPR cas9)--all in an easy-to understand book.

E-Textbook For Better Learning In Chemistry 120, Anh Vu '27, Jeffery A. Hansen

Annual Student Research Poster Session

Organic chemistry is a highly visual subject since organic compounds are 3D objects. For this reason, in order to fully understand the composition, properties, and chemistry of these compounds, it is essential to understand and visualize their 3D structures. Nevertheless, there is a frequent necessity to depict organic substances on 2D surfaces, such as paper, a computer screen, or a whiteboard. As a result, one of the biggest obstacles we will face is learning these molecules in a 2D format while maintaining an accurate understanding of 3D nature. The purpose of this e-textbook is to fully utilize the digital medium …

Computational Analysis Of O6-Methylated Guanine And Thioguanine Complexes, Kirsten Stinson, Michael Bowman

Lux et Fides: A Journal for Undergraduate Christian Scholars

DNA methylation occurring on the O⁶ position of guanine has been linked to the formation of cancer. DNA complexes with O⁶-methylated guanine have been studied experimentally, yet questions remain concerning the carcinogenic properties of O⁶-methylguanine. This present research explored the interaction between O⁶-methylguanine and its potential nucleobase pairs of cytosine and adenine in hopes of elucidating the mutagenic characteristics of O⁶-methylguanine. A variety of computational methods including Density Functional Theory (DFT), Symmetry Adapted Perturbation Theory (SAPT), Noncovalent Interaction (NCI) analysis, and Natural Bond Orbital (NBO) analysis were employed to comprehensively probe …

Mycobacteriophage Lberry, An A3 Cluster Phage Infecting Mycobacterium Smegmatis, Nathan Berry '25

Chemistry & Biochemistry Student Scholarship

Nathan Berry ’25, Biochemistry major
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Synthesis Of 2-Substituted Beta-Carbolines From N-Oxides, Alma Martinez '26

Chemistry & Biochemistry Student Scholarship

Alma Martinez ’26, Biochemistry major
Faculty Mentor: Dr. Seann Mulcahy, Chemistry and Biochemistry

Mycobacteriophage Maravista, An F1 Cluster Phage Infecting Mycobacterium Smegmatis, Charles Pelagalli '25

Chemistry & Biochemistry Student Scholarship

Charles Pelagalli ’25, Biochemistry major
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Mycobacteriophage Rita, Anna Fakhri '24

Chemistry & Biochemistry Student Scholarship

Anna Fakhri ’24, Biochemistry major
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Mycobacteriophage Pembroke, An A3 Cluster Phage Infecting Mycobacterium Smegmatis, Marly Cassford '25

Chemistry & Biochemistry Student Scholarship

Marly Cassford ’25, Biochemistry major
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Genome Announcement For E Cluster Phage Tarkin, Katherine Cleary

Chemistry & Biochemistry Student Scholarship

Katherine Cleary ’23
Major: Biochemistry
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Purification And Kinetic Characterization Of Mutant R111v Human Cytosolic Malate Dehydrogenase, Jackson Demartino

Chemistry & Biochemistry Student Scholarship

Metabolic profiling for a variety of cancerous cells indicate significant increases in the levels of glucose consumption. To support uncontrolled cell division, cancer cells also present an uncoupling of glycolysis from the citric acid cycle to promote glucose carbons to the synthesis of biomass, therefore, requiring a constant supply of NAD⁺. Recent studies indicate that cancer cells exhibit upregulated cytosolic malate dehydrogenase (MDH1) activity, which catalyzes the conversion of oxaloacetate to malate with the oxidation of NADH, generating NAD⁺. Given its increased activity, MDH1 may serve as a valuable target for treating cancer. Here we report …

Synthesis Of Trifluoromethyl Ketones By (Diethylamino) Sulfur Trifluoride (Dast)-Mediated Nucleophilic Trifluoromethylation Of Benzoic Acids, Michael A. Vescio

Honors College Theses

Within the past few decades, the presence of fluorine containing

organic molecules has increased significantly. Many of the

current industrial production methods are not cost-effective,

practical, or inherently safe. This work describes a new methodology

for the synthesis of trifluoromethyl ketones. Our new method involves

the use of benzoic acid and trifluoromethyl trimethylsilane (TMSCF₃) as starting

materials along with diethylamino sulfur trifluoride (DAST) as a reagent

to obtain moderate to good yields of expected products in a short

reaction times.

Case 59: Inhibition Of Enzymes Involved In Steroid Synthesis: Implications In Diabetes Treatment, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

Drugs used to increase insulin sensitivity may also inhibit enzymes involved in steroid synthesis. Prior to this investigation, it was uncertain whether the drugs inhibited the enzymes directly or whether the decrease in androgen synthesis observed during treatment was a secondary effect.

Targeting Heat Shock 27 Kda Protein Induces Androgen Receptor Degradation, Yaxin Li

ETD Archive

Glioblastoma (GBM) is the most common and aggressive brain tumor, with very poor prognosis. Androgen receptor (AR) plays a significant role in the progression of GBM, and anti-androgen agents have the potential to be used for the treatment of GBM. However, AR mutation commonly happens in GBM, which makes the anti-androgen agents less effective. Heat shock 27 kDa protein (HSP27) is a well-documented chaperone protein to stabilize AR. Inhibition of HSP27 results in AR degradation regardless the mutation status of AR, which makes HSP27 a good target to abolish AR in GBM. Identified compound I ((N-(3-((2,5-dimethoxybenzyl)oxy)-4-(methylsulfonamido) phenyl)-4-methoxybenzamide) inhibits GBM cell …

Exploring Indicator Displacement Assays For Phosphate Detection In Seawater, Francis Radics

Chemistry & Biochemistry Student Scholarship

Francis Radics ’22
Major: Biochemistry
Faculty Mentor: Dr. John Breen, Chemistry and Biochemistry

Indicator displacement assays are based on the optical signal modulation of a noncovalently bound indicator upon dissociation by an analyte species. Our work has focused on exploring the lower detection limits for luminescent displacement assays for inorganic phosphate in seawater using complex ions containing two di(2-picolyl)amine ligands (also called DPA or bis(2-pyridylmethyl)amine), each coordinating a zinc cation. Following the work of B.D. Smith and coworkers, we have prepared three ligands by covalently attaching two DPA moieties, 2,6-bis(chloromethyl) benzene, and 2,6-bis(chloromethyl)-4-methylphenol, and 1,2-phenylenedimethylamine, for assays with 6,7-dihydroxy-4-methanesulfonic acid …

Proline To Serine Mutation In The Active Site Loop Of Malate Dehydrogenase Alters Substrate Specificity, Olivia J. Schmitt

Chemistry & Biochemistry Student Scholarship

Cancer cells preferentially undergo glycolysis in aerobic environments, a phenomenon termed the Warburg effect. Malate dehydrogenase (MDH) catalyzes the reversible interconversion of malate and oxaloacetate. Human cytosolic malate dehydrogenase (hMDH1) isoform 3 is involved in the malate-aspartate shuttle (MAS), which oxidizes cytosolic NADH. hMDH1 is implicated in high aerobic glycolysis in cancer cells because NAD is a necessary cofactor for glycolysis. Thus, hMDH1 is a promising molecular target for cancer treatment. A single proline residue at position 110 in the mobile active site loop of hMDH1 was mutated to a serine with the intention of altering the enzyme’s substrate specificity. …

Development And Kinetic Survey Of A G148t Mutant Human Cytosolic Malate Dehydrogenase Isoform 3 Enzyme With Oxaloacetate And A-Ketoglutarate, Ethan N. Dionne

Chemistry & Biochemistry Student Scholarship

Cancer cells often use an altered metabolic pathway in which glycolysis, uncoupled from the citric acid cycle, serves as the primary source of ATP. To support cancer cell proliferation and growth, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) must have a constant source of NAD. While lactate dehydrogenase (LDH) in its conversion of pyruvate to lactate is a well-known source of cytosolic NAD for GAPDH activity, cytosolic malate dehydrogenase (MDH1) also plays a role in cell proliferation through its generation of cytosolic NAD by the conversion of OAA to malate. This development has implicated MDH1 in cancer cell metabolism and characterizing …

Case 71: Lactate Dehydrogenase As A Therapeutic Target To Treat Parasitic Disease, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

In this case study, researchers use their knowledge of lactate dehydrogenase in parasites and humans to investigate inhibitors that are selective for the parasite agent.

Initial Characterization Of Prna From Burkholderia Ambifaria: Developing An Nadph-Dependent Activity Assay For Tryptophan Halogenation, Mahmuda Akter

Theses and Dissertations

Some bacteria produce a potent antifungal agent (pyrrolnitrin) from tryptophan using four dioxygen dependent steps to outcompete other microbes. Each step of this process is catalyzed by an oxygenase encoded by the prnABCD cassette. The first enzymatic step in pyrrolnitrin biosynthesis is the regioselective chlorination of tryptophan to form 7-chlorotryptophan. This halogenation is catalyzed by PrnA, a Flavin dependent oxygenase, which has been isolated and characterized from P. fluorescens. The pyrrolnitrin biosynthesis pathway (prnABCD) has been also observed in the Burkholderia genus. This thesis comprises my studies on the expression, purification, and characterization of PrnA from Burkholderia ambifaria. Beyond the …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Case 51: Purification Of A Transferase Involved In The Production Of Physiologically Important Glycoproteins, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

A transferase involved in post-translational glycosylation of a physiologically important glycoprotein is purified and characterized.

Case 40: A Collection Of Collagen Cases, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

Factors important in the stability of collagen are examined.

Case 6: Hemoglobin Providence, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

A mutant hemoglobin variant, Hemoglobin Providence, exists in two forms in vivo.