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Articles 1 - 12 of 12
Full-Text Articles in Medical Biochemistry
Engineering Enac Constructs To Examine Pip2 And Ubiquitin Competition On Enac Regulation And Stability, Lacie Johnson
Engineering Enac Constructs To Examine Pip2 And Ubiquitin Competition On Enac Regulation And Stability, Lacie Johnson
Chemistry & Biochemistry Undergraduate Honors Theses
The epithelial sodium channel (ENaC) plays a critical role in sodium homeostasis, fluid balance, and blood pressure regulation. ENaC activity is tightly controlled by post-translational mechanisms, including ubiquitination-mediated degradation and phosphatidylinositol 4,5-bisphosphate (PIP2) dependent channel activation. PIP2 is a phospholipid necessary to facilitate the maximal channel opening. Previous studies suggest that intracellular PIP2 binding sites are located in proximity to ubiquitination sites on ENaC subunits, raising the possibility of PIP2 binding to influence channel stability and function. This thesis aimed to engineer and validate molecular tools capable of examining the interplay between PIP2 binding and ubiquitination in ENaC regulation. A …
Exploring The Metabolic And Mitogenic Potential Of A Hyper-Stable Variant Of Fgf1, Emma Starr, Oshadi Edirisinghe, Thallapuranam Krishnaswamy Suresh Kumar
Exploring The Metabolic And Mitogenic Potential Of A Hyper-Stable Variant Of Fgf1, Emma Starr, Oshadi Edirisinghe, Thallapuranam Krishnaswamy Suresh Kumar
Inquiry: The University of Arkansas Undergraduate Research Journal
Fibroblast growth factors (FGFs) are a family of 22 human cytokines involved in critical cellular processes, such as proliferation, differentiation, metabolism, angiogenesis, tumor metastasis, and wound healing. Among these, fibroblast growth factor 1 (FGF1) possesses a powerful mitogenic potential as it can nonspecifically bind to all four FGF receptors. However, the therapeutic applications of FGF1 are hindered by its inherent thermal and proteolytic instability, especially at physiological temperatures. This is believed to be attributed to the heparin-binding pocket at the C-terminus, which contains numerous positively charged residues that repel each other. To combat this instability, FGF1 binds to a negatively …
Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman
Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman
Chemistry & Biochemistry Undergraduate Honors Theses
The FGF-1 subfamily, composed of FGF-1 and FGF-2, assists in broad health-related processes such as cell proliferation and angiogenesis respectively.1,2 The subfamily shows promising signs as a therapeutic, however, the inherent thermal instability leads to a low half-life in vivo.3 To assist in improving the stability, FGF-1 and FGF-2 were connected via a 12-residue glycine linker ultimately producing a heterodimer. This heterodimer was further examined to discover its novel properties. Inspiration for this project was drawn from previous research which performed five mutations on FGF-1 ultimately improving stability in the protein complex. In addition to these five …
An Investigation On The Effect Of Conserved Hinge Histidine On Influenza Hemagglutinin(Ha2) Protein Conformation Using Md Simulations, Nada Tolba
Chemistry & Biochemistry Undergraduate Honors Theses
Hemagglutinin is a protein on the surface of Human Influenza Viruses.1 It is composed of two glycopolypeptide domains, the HA1 and HA2 domains. Previous studies have found that across different strains of Influenza viruses, HIS435 residues remain conserved.4 In studies where mutations occurred in hinge-site histadine residues, the Influenza virus was inactive.4 These investigations indicated a significant role of HIS435 (hinge-site histadines) in virulence. Four systems were created using Molecular dynamics (MD) simulations. Each system was composed of an Isolated HA2 trimer solvated in a 150 mM NaCl rectangular water box at 310 K under isobaric and …
Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder
Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder
Graduate Theses and Dissertations
Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …
Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza
Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza
Graduate Theses and Dissertations
The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …
Design Of Hfgf1 Variant(S) With Increased Stability And Enhanced Bioactivity, Shilpi P. Agrawal
Design Of Hfgf1 Variant(S) With Increased Stability And Enhanced Bioactivity, Shilpi P. Agrawal
Graduate Theses and Dissertations
Fibroblast growth factors (FGFs) are involved in various cellular processes such as cell growth,proliferation, differentiation, migration, angiogenesis, wound healing and embryonic development. Human acidic fibroblast growth factor (hFGF1) binds non-selectively to all the four FGF-receptors and is therefore considered as a powerful mitogen with broadest specificity. However, pharmacological applications of hFGF1 are restricted due to the low thermal stability of the growth factor. hFGF1 has low thermodynamic stability under physiological temperatures which leads to impairment of cellular signaling process thereby preventing its potential mitogenic properties. hFGF1 has a heparin binding pocket at the C-terminus which comprises of positively charges residues. …
Instrumental Aspects Of Oxygen Sensing: Quantitation And Recalibration Of A Biofouled Oxygen Sensor, Marlena Patrick
Instrumental Aspects Of Oxygen Sensing: Quantitation And Recalibration Of A Biofouled Oxygen Sensor, Marlena Patrick
Graduate Theses and Dissertations
In vivo oxygen sensing is a critical area of research for medical applications, such as ischemic stroke, but this important topic is not fully understood or resolved. In addition, the best method for calibration of in vivo sensors is as yet undetermined. For all implantable devices, biofouling, the adsorption of biological material to the device surface, is another significant problem with no clear or well-defined solution. One method employed is to apply a protective polymer membrane to the sensor surface in order to minimize the adsorption of biological material. The work described here investigates two polymers applied to a gold …
Deciphering The Role Of Glycine134 In The Human Acidic Growth Factor-1’S Binding To Heparin, Adam W. Burroughs
Deciphering The Role Of Glycine134 In The Human Acidic Growth Factor-1’S Binding To Heparin, Adam W. Burroughs
Chemistry & Biochemistry Undergraduate Honors Theses
Human acidic fibroblast growth factor 1 (FGF-1) is a potent modulator of cell survival and exhibits a universal role in various physiological processes. Though potent, FGF-1 unbound to heparin is known to show a poor thermal stability and a relatively short in vivo half-life. Much is known about the structure and relation of FGF-1 with heparin yet there is still unknown information regarding the exact role of heparin in stabilizing FGF-1. Thus, the aim of this study is to mutate glycine at position 134 to glutamic acid in wild type FGF1. G134 is located in the heparin binding pocket, thus …
Peptoid Based Slide Coatings For Disease Detection Via Elisa Microarray Analysis, Melissa Lea Hebert
Peptoid Based Slide Coatings For Disease Detection Via Elisa Microarray Analysis, Melissa Lea Hebert
Graduate Theses and Dissertations
Poly-N-substituted glycines (peptoids) are a very versatile family of synthetic molecules that can be customized for any number of applications. In this study, we chose to use peptoids as a foundation for sandwich ELISA microarray analysis with a long term goal of creating an early detection device for complex diseases such as cancer. The peptoids were designed to self-assemble into microspheres to be used in coatings on the surface of the microarray substrates to increase the surface area available for antibody attachment. This increased antibody density would lead to an increase in the microarray analysis sensitivity and dynamic range. Studies …
Development Of A Microfluidic Device Coupled To Microdialysis Sampling For The Pre-Concentration Of Cytokines, Randy Francisco Espinal Cabrera
Development Of A Microfluidic Device Coupled To Microdialysis Sampling For The Pre-Concentration Of Cytokines, Randy Francisco Espinal Cabrera
Graduate Theses and Dissertations
A proof-of-concept microfluidic device combined with heparin-immobilized magnetic beads was created to concentrate cytokine proteins collected from microdialysis samples. Cytokines are known to be related to several diseases such as cancer, and Parkinson's diseases, so to be able to develop more effective diseases treatments their interactions have to be well understood. Amine-functionalized polystyrene and carboxyl-functionalized magnetic microspheres of ~6.0 ìm in diameter were used to immobilize heparin. The amount of heparin immobilized on polystyrene beads was 5.82 x 10-8 ± 0.36 x 10-8 M per 1.0 x 106 beads and for magnetic beads was 0.64 x 10-8 ± 0.01 x …
Synthesis And Chemistry Of Naphthalene Annulated Trienyl Iron Complexes: Potential Anticancer Dna Alkylation Reagents, Traci Means
Synthesis And Chemistry Of Naphthalene Annulated Trienyl Iron Complexes: Potential Anticancer Dna Alkylation Reagents, Traci Means
Inquiry: The University of Arkansas Undergraduate Research Journal
Iron complex chemistry that opens a new door to the medicinal and pharmaceutical worlds is the aim of this research. Specifically, ortho-quinone methide moieties are intermediates in several antitumor drugs and have been identified as bioreductive alkylators of DNA. In our research, a class of iron compounds has been targeted to resemble these quinone methides. It is hoped that these new compounds could be modified to provide a window of opportunity toward the discovery of a selective mode of drug delivery. We have focused our efforts on generating a reactive transition metal complexed 5-membered ring analog of o-quinone methide based …