Biochemistry Commons^™

Dual Ionic Liquid-Functionalized Cellulosic Materials: Thermal, Mechanical And Conductive Properties, Elizabeth Mcgrew, Kevin M. Miller Phd

Posters-at-the-Capitol

Cellulose, an inexpensive and renewable biomacromolecule, represents an intriguing synthetic foundation for new materials with task-specific properties. Here, we wish to report a synthetic route for functionalizing cellulose with a side chain containing two ionic liquid functional groups using azide-alkyne ‘click’ cyclization strategy, followed by quaternization of the two resulting heterocycles (1,2,3-triazole and imidazole). Through this functionalization strategy, the resulting cellulosic materials exhibited significant softening, with several glass transition (T_g) values observed below room temperature, indicating the amorphous nature of the materials, with the T_g dependent on both the length of the side chain and the …

Cellular Zinc Deficiency Impairs Heme Biosynthesis In Developing Erythroid Progenitors, Juyoung Kim, Jaekwon Lee, Moon-Suhn Ryu

Department of Biochemistry: Faculty Publications

Anemia is the most prevalent nutrition-related disorder worldwide. Zinc is an essential trace element for various biological processes in the body, and zinc deficiency has been associated with anemia in humans. However, the molecular mechanisms by which zinc availability alters red blood cell development remain uncertain. The present study identifies the essentiality of zinc during erythroid development, particularly for normal heme biosynthesis. G1E-ER4 mouse cells were used as an in vitro model of terminal erythroid differentiation, which featured elevated cellular zinc content by development. Restriction of zinc import compromised the rate of heme and -globin production and, thus, the hemoglobinization …

Progress Towards The Total Synthesis Of Frondosin D Lab Report, Admirabilis Kalolella

CISLA Senior Integrative Projects

No abstract provided.

Characterization Of Cl-Par-4: Wt Vs. Mutant, Samjhana Pandey, Krishna K. Raut, Andrea M. Clark, Antoine Baudin, Lamya Djemri, David S. Libich, Steven M. Pascal

The Graduate School Posters

Intrinsically disordered proteins (IDPs) play important roles in regulation of cell signaling pathways as well as cellular processes. Dysregulation of these proteins is associated with several human diseases. Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is categorized as an intrinsically disordered protein and downregulation of this protein has been reported in myriad of cancers including glioma, breast cancers, and prostate cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) plays an active role in tumor suppression by inhibiting several cell survival pathways.

Here, we employed site-directed mutagenesis to introduce a point mutation in the cl-Par-4 wildtype (WT) to generate the …

Using Nspefs To Sensitize Mrsa To Vancomycin Treatment, Areej Malik, Alexandra E. Chittams-Miles, Claudia Muratori, Erin B. Purcell

The Graduate School Posters

Staphylococcus aureus (S. aureus) is a biofilm-forming pathogen. S. aureus treatment is marked by the development of antibiotic resistance. The public health impact has increased since the emergence of methicillin-resistant S. aureus (MRSA), which has started to show intermediate resistance to vancomycin in MRSA. Nano-second pulse electric fields (nsPEFs) are low-energy and high-power electric pulses, which have been suggested to sensitize pathogens to antibiotics by creating transient pores in the cell membrane. Our combinatorial treatment includes nsPEF pre-treatment and vancomycin post-treatment of MRSA cells. Our results show that MRSA log phase cells had the highest susceptibility to vancomycin. …

Par-4: An Attractive Target For Cancer Therapy, Krishna K. Raut, Antoine Baudin, David S. Libich, Lijun Liu, Scott Lovell, Steven M. Pascal

College of Sciences Posters

Lack of early diagnosis, cancer recurrence, metastasis, and adverse side effects are some of the major problems in the treatment of cancers. Par-4, a tumor suppressor protein, is an attractive target for cancer therapy as it selectively kills cancer cells. Cl-Par-4 is the active fragment of Par-4 that enters the nucleus and selectively induces apoptosis in cancer cells. It has also been reported that Par-4 increases the susceptibility of cancer cells to chemotherapy and reverses cancer recurrence. Further, Par-4 has been shown to play a dual role: inhibition of EMT (Epithelial-mesenchymal transition) as well as assistance in the reverse process, …

Mechanistic Insights Into Mftr-Dependent Regulation Of The Redox Cofactor Mycofactocin, Aigera Mendauletova

Electronic Theses and Dissertations

Organic redox cofactors are essential for life. While classic flavins and nicotinamides are widely distributed across all domains of life, nature has also evolved niche cofactors in subsets of life domains. For example, in Actinobacteria, coenzyme F420 is commonly used in place of flavin mononucleotide in enzymes associated with carbon fixation and oxidation of secondary alcohols. The importance of niche cofactors has long been recognized however, detailed understanding about their biosynthesis and physiological uses has been lagging. One class of niche cofactors is derived from ribosomally synthesized and posttranslationally modified peptides (RiPPs). To achieve their mature form, the genetically …

Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms, Shreya Nagar

Theses and Dissertations

The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. Major part of DDR is coordinated by DNA damage checkpoint (DDC). In addition to DDC, eukaryotic cells also have DNA replication checkpoint (DRC) that is distinct from the DDC and specifically signals slowly progressing or arrested replication forks. DDR involves stalling or arrest of the cell cycle, initiation of DNA repair, and altered regulation of transcription, translation, and the ubiquitin-proteasome system. DDR also triggers transcription shut-off of histone genes. One of the key outcomes of DDC/DRC activation is the increased synthesis of the deoxyribonucleoside triphosphates (dNTPs), …

Temperature Effects On Conductivity Of Phospholipid Bilayers, Dylan Mount, Sebastian Grabill, Loren Haarsma

Summer Research

Phospholipids molecules contain a fatty acid tail and a head made of a phosphate group (Fig.1) and serve as the building blocks of cellular membranes. The tails are hydrophobic, meaning they are weakly attracted to water, while the head group is hydrophilic, which is strongly attracted to water. Lipids in water will spontaneously form into bilayers with the tails towards the center (Fig.2) and the heads pointing towards the water on either side. This is how the lipid bilayers are formed to separate a cell's interior from exterior. Biological cells contain mixtures of many lipids and other molecules. In our …

Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …

Alterations In C:N Ratio To Understand Plant Metabolic Pathways In Response To Pressure From Goat Grazing In The Invasive Species: Rhamnus Cathartica, Vivian Marchan

Ignite the Spark Outstanding Undergraduate Research and Scholarship

The high fecundity and high germination rates of Rhamus cathartica serves the species to out-compete regional plant native species. Its high abundance in deciduous forest ecosystems forces species that are unable to utilize R. cathartica as a food source to migrate to areas of lower density, further contributing to the decline in regional biodiversity. Bare soil conditions left as the result of the high concentration of Nitrogen in senesced leaves and leaf litter, cause further amplification of the migration of non-plant species to areas of lower R. cathartica density. Nitrogen is essential to primary and secondary metabolism, thus minimizing the …

Post-Translational Modification Of Proteins Via Ambient Air Pollutants And Endogenous Reactive Species, Rachel Lauren Davey

Electronic Theses and Dissertations

Proteins can react with reactive oxygen species (ROS) and reactive nitrogen species (RNS) to form post-translational modifications (PTMs), which can affect protein structure and function. The formation of 3-nitrotyrosine (NTyr) and dityrosine (DiTyr) upon reaction of proteins with ROS/RNS are two common PTMs studied due to their stability and irreversibility, as well as their ability to enhance the allergenicity of pollen allergens upon formation. Many common techniques used to study the formation of these PTMs can reliably detect the PTMs but can only provide semi-quantitative information due to many assumptions and limitations. In Chapter 2 we present an analysis of …

Selective Reduction Of Nitriles In The Presence Of Aromatic Nitro Groups, Esther Seoha Yoo, Dr. Michael Barbachyn

Summer Research

• Identify reliable aprotic reaction conditions for selective reduction of a nitrile in the presence of a nitro group. •
• Examine a range of nitrobenzonitriles and nitrophenyl acetonitriles to determine the scope of the methodology.

Investigating Peptide Folding Of Tryptophan Zippers, Chad Tatko, Jessica Bedow, Kachel Bedow, Maddy Hoogstra, Douglas Vander Griend

Summer Research

Protein folding has been a subject of interest in the research community for its wide array o f applications in academia and medicine. By understanding how the interaction of localized amino acids in different environmental factors affect the global folding of peptides, one can anticipate synthesis of proteins or manipulation of exis ting pro teins to have more desirable functions. For this investigation, tryptophan zippers (monomeric β-hairpin peptides) were synthesized, titrated in differing pH, and analyzed by NMR

Purification Of Anginex: An Inhibitor Of Tumor Metastasis Using Rdrd Tag, Suraj Kolluru

Inquiry: The University of Arkansas Undergraduate Research Journal

Anginex is a cytokine-like β-sheet forming peptide of 33 amino acids with potent anti-angiogenic activity.Anginex is essential in inhibiting abnormal processes caused by angiogenesis, such as tumor growth and blood vessel formation. However, Anginex has limitations, including poor stability, short half-life, complicated synthesis, and low purity. Rubredoxin dimer (RdRd) is used as a protein tag to improve stability and detection of Anginex during purification for the first time. A plasmid was designed to contain the RdRd-Anginex fusion protein. RdRd-Anginex plasmid was transformed and expressed in E. coli BL21star cells. The results show RdRd-Anginex has been purified using a Nickel Sepharose …

Novel Application Of Graphene Oxide In Conjunction With Dna Binding Dcas9 For Detecting Antibiotic Resistance Genes, Langley Williams

Mahurin Honors College Capstone Experience/Thesis Projects

The frequent emergence of antibiotic resistance genes poses a stumbling block to prompt treatment of pathogen-originating diseases and therefore spurs the demand for a simple, rapid diagnostic device that can outcompete the time and cost of traditional methods such as PCR and cell culturing. The proposed method for detecting pathogenic DNA utilizes the binding properties of deactivated CRISPR-associated protein9 (dCas9) complexed with fluorescein-labeled single-guide RNA (sgRNA) and the fluorescence quenching properties previously demonstrated in graphene oxide (GO). For our assay, we designed sgRNAs to target specific 20 nucleotide sequences extracted from the tetracycline resistance (tetM) gene sequence and covalently modified …

Chemistry And Public Policy: Equipping Advocates, Herbert R. Fynewever, I. Bos, C. Demlow, G. Fulkerson

Summer Research

No abstract provided.

The Effects Of Exogenously Applied Antioxidants On Plant Growth And Resilience, Aline Rodrigues De Queiroz, Connor Hines, Jeremy Brown, Seema Sahay, Jithesh Vijayan, Julie M. Stone, Nate Bickford, Melissa Wuellner, Katarzyna Glowacka, Nicole R. Buan, Rebecca Roston

Department of Biochemistry: Faculty Publications

Plant growth and resilience require balancing an inherently oxidative metabolism with powerful antioxidant systems that help maintain homeostasis. When the environment changes, reactive oxygen species are potent indicators of that change, allowing adaptation through re-balancing metabolism and antioxidant systems. A large body of evidence supports the use of exogenously applied antioxidants to improve both plant growth and their resilience to stress. Notably, some phenotypic effects are similar upon the application of chemically diverse antioxidants, while others are distinct. In this review, we analyze research from antioxidant treatment experiments and highlight the similarities in their practical applications and their effects on …

Botanical Assessment Of Remnant Floodplain Habitats Along Plaster Creek, Kent County, Michigan: Assessing Changes Since The 1890s, Haley R. Weesies, Garrett Crow, David Warners

Faculty and Professional Research

Plaster Creek, a tributary of the Grand River, drains a 58-square mile watershed in Kent County, Michigan. Its headwaters originate in the agriculturally dominated southwestern portion of the county, and then it meanders through residential, commercial, and urban areas of Kentwood and Grand Rapids before it empties into the Grand River about one mile south of downtown Grand Rapids. Much of Plaster Creek’s original floodplain, like the rest of its watershed, has been drastically altered and degraded over time due to the development of residential neighborhoods, commercial properties, agriculture, and industrial zones. Floodplains house unique assemblages of Michigan’s native biodiversity …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …

Following Faculty Engaging In Collaborative Action Research To Approach Curricular Change In Undergraduate Biochemistry, Christopher Nix

Electronic Theses and Dissertations, 2020-2023

This study engaged in a curricular redesign of an undergraduate biochemistry course undertaken by a collaborative action research group. The initial portion of this study investigated student conceptual understanding of foundational concepts via a rigorously tested concept inventory. the impact of the redesign on the student foundational conceptual understanding was determined by comparison with a baseline data set. Findings suggest that students enter and exit the biochemistry course with little understanding of key foundational concepts. Examination of student performance after the incorporation of creative exercises showed a significant impact of the curricular changes on two of the concepts of interest. …

Tagging Atg5 With An Epitope Tag To Measure The Amount Of Atg12-5 Conjugation In Atg10 Mutants, Sophie Campbell

Senior Honors Theses and Projects

Autophagy is a necessary recycling process that occurs in cells, but the functions of the proteins that carry this out are not completely understood. The protein ATG10 has a distinct role in forming autophagosomes, large double membrane vesicles necessary for this process. ATG10 forms a covalent bond between the proteins ATG12 and ATG5 but its final effect on autophagosome formation is still unclear. We are using DNA manipulation techniques to add a myc epitope tag to yeast ATG5 which will allow us to measure the effect of atg10 mutants on ATG12-5 conjugation via Western Blot. These results will help us …

Establishing A Biochemical System For The Purification And Atpase Activity Of Gst-Dbp5, Sarah Utley, Rachel E. Rigsby Phd, Rebecca L. Adams Phd

Science University Research Symposium (SURS)

The export of mRNA out of the nucleus is a crucial step for eukaryotic gene expression. The export of mRNA transcripts is aided by Mex67, which allows export through the nuclear pore complex doorways in the nuclear envelope. Once out of the nucleus, a protein known as Dbp5, bound to ATP, Gle1, and Nup42 aids in the directionality of mRNA export by helping remove Mex67 from the mRNA strand. Following interaction with RNA, Dbp5 then hydrolyzes ATP so that it unbinds the mRNA, allowing for enzyme recycling. The goal of this study is to explore the ATPase activity of Saccharomyces …

Identification Of Rickettsia Prowazekii Methionine Aminopeptidase Inhibitors And Development Of Thermal Shift Assays For Burkholderia Pseudomallei Ispf And Sars-Cov-2 3cl Protease, Ishpriya Sharma

Graduate Research Theses & Dissertations

There is a crucial need for new antibacterial agents to combat the increase in antibiotic resistance. Methionine aminopeptidase (MetAp) is an enzyme that removes the amino-terminal methionine residue from newly synthesized proteins, an important step in the maturation of proteins. As such, MetAp is a target for the development of antibacterial and anticancer agents. One such bacterial target is Rickettsia prowazekii (Rp), the causative agent of epidemic typhus. To discover new inhibitors of RpMetAp1, the MMV Malaria Box, which is a collection of 400 compounds with drug-like and probe-like compounds, was screened using a high throughput fluorescence-based RpMetAp1 enzyme inhibition …

Structure–Activity Relationship Studies On 6-Chloro-1-Phenylbenzazepines Leads To The Identification Of A New Dopamine D1 Receptor Antagonist, Rajan Giri, Hari K. Namballa, Vishwashiv Emogaje, Wayne W. Harding

Publications and Research

The 1-phenylbenzazepine template has yielded a number of D1R-like ligands, which, though useful as pharmacological tools, have significant drawbacks in terms of selectivity versus D5R as well as pharmacokinetic behavior. A number of 1-phenylbenzazepines contain a 6-chloro functional group, but extensive SAR studies around the 6-chloro-1-phenylbenzazepine framework have not been reported in the literature. To further understand the tolerance of the 6-chloro-1-phenylbenzazepine template for various substituent groups towards affinity and selectivity at D1R, we synthesized two series of analogs with structural variations at the C-7, C-8, N-3, C-3′ and C-4′ positions. The series 2 analogs differed from …

Plastic Recognition And Electrogenic Uniport Translocation Of 1st-, 2nd-, And 3rd-Row Transition And Post-Transition Metals By Primary-Active Transmembrane P1b-2-Type Atpase Pumps, Sameera S. Abeyrathna, Nisansala S. Abeyrathna, Priyanka Basak, Gordon W. Irvine, Limei Zhang, Gabriele Meloni

Department of Biochemistry: Faculty Publications

Transmembrane P-type ATPase pumps catalyze the extrusion of transition metal ions across cellular lipid membranes to maintain essential cellular metal homeostasis and detoxify toxic metals. Zn()-pumps of the P-type subclass, in addition to Zn , select diverse metals (Pb, Cdand Hg) at their transmembrane binding site and feature promiscuous metal-dependent ATP hydrolysis in the presence of these metals. Yet, a comprehensive understanding of the transport of these metals, their relative translocation rates, and transport mechanism remain elusive. We developed a platform for the characterization of primary-active Zn()-pumps in proteoliposomes to study metal selectivity, translocation events and transport mechanism in real-time, …

The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku

Biotechnology Theses

Lung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the …

Isotopic Evidence For Sources Of Dissolved Carbon And The Role Of Organic Matter Respiration In The Fraser River Basin, Canada, Britta M. Voss, Timothy I. Eglinton, Bernhard Peucker-Ehrenbrink, Valier Galy, Susan Q. Lang, Cameron Mcintyre, Robert G.M. Spencer, Ekaterina Bulygina, Zhaohui Aleck Wang, Katherine A. Guay

OES Faculty Publications

Sources of dissolved and particulate carbon to the Fraser River system vary significantly in space and time. Tributaries in the northern interior of the basin consistently deliver higher concentrations of dissolved organic carbon (DOC) to the main stem than other tributaries. Based on samples collected near the Fraser River mouth throughout 2013, the radiocarbon age of DOC exported from the Fraser River does not change significantly across seasons despite a spike in DOC concentration during the freshet, suggesting modulation of heterogeneous upstream chemical and isotopic signals during transit through the river basin. Dissolved inorganic carbon (DIC) concentrations are highest in …

การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีนในวิถีวิตามินดีและความเสี่ยงต่อภาวะออทิซึมสเปกตรัมในประชากรไทย, ชาญณรงค์ แซ่ฉั่ว

Chulalongkorn University Theses and Dissertations (Chula ETD)

กลุ่มอาการออทิซึมสเปกตรัม (Autism spectrum disorder; ASD) เป็นปัญหาสุขภาพระดับโลกที่สำคัญ โดยพบว่ามีความชุกของโรคที่เพิ่มสูงขึ้น อย่างไรก็ตามสาเหตุและกลไกในการเกิดภาวะออทิซึมสเปกตรัมยังไม่ทราบแน่ชัดอาจเกี่ยวข้องกับปัจจัยด้านพันธุกรรมและสิ่งแวดล้อม โดยปัจจุบันมีรายงานถึงบทบาทของวิตามินกับภาวะออทิซึมสเปกตรัม วัตถุประสงค์ของการศึกษานี้คือศึกษาการเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีนในวิถีเมทาบอลิกของวิตามินดีและความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมและระดับความรุนแรงของโรคในเด็กไทย การศึกษานี้มีจำนวนอาสาสมัคร 276 ราย โดยเป็นกลุ่มเด็กที่มีภาวะออทิซึมสเปกตรัม 169 ราย และกลุ่มควบคุมเป็นเด็กที่ไม่มีโรคทางระบบประสาท 107 ราย ซึ่งได้ทำการตรวจวิเคราะห์ภาวะพหุสัณฐานทางพันธุกรรมของยีน CYP2R1, CYP27B1, GC และ VDR โดยเทคนิค TaqMan-based real-time Polymerase Chain Reaction (PCR) และตรวจวิเคราะห์ระดับวิตามินดีในกระแสเลือดโดยใช้เทคนิค Chemiluminescence Immunoassay (CLIA) โดยเด็กที่พบภาวะออทิซึมสเปกตรัมจะได้รับการตรวจระดับความรุนแรงของภาวะออทิซึมสเปกตรัมด้วย Childhood Autism Rating Scale, 2nd Edition (CARS2) โดยผลที่ได้จากการศึกษาพบว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน CYP2R1, CYP27B1, VDR และ GC (rs4588) ไม่มีความสัมพันธ์กับการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัม อย่างไรก็ตามการศึกษาชี้ให้เห็นว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน GC (rs7041 (A>C)) มีความสัมพันธ์อย่างมีนัยสำคัญกับความเสี่ยงที่เพิ่มขึ้นต่อการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัมด้วย โดยเฉพาะอย่างยิ่งบุคคลที่มีการขาดระดับวิตามินดีร่วมด้วย นอกจากนี้ผลศึกษาพบว่าไอโซฟอร์มของ GC1s และ GC1s-GC1s ฟีโนไทป์มีความสัมพันธ์อย่างมีนัยสำคัญกับความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมตลอดจนความรุนแรงของอาการออทิซึมสเปกตรัม โดยสรุปการศึกษาวิจัยในครั้งนี้ชี้ให้เห็นว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน GC (rs7041 (A>C)) และไอโซฟอร์ม GC1s อาจเป็นตัวบ่งชี้ทางพันธุกรรมที่สามารถช่วยในการประเมินความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัมในเด็กไทยได้ในอนาคต อย่างไรก็ตามการศึกษาในอนาคตควรศึกษาในกลุ่มประชากรที่ใหญ่ขึ้นเพื่อยืนยันผลการศึกษาวิจัยครั้งนี้

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …