Amino Acids, Peptides, and Proteins Commons^™

Allosteric Control Overcomes Steric Limitations For Neutralizing Antibodies Targeting Conserved Binding Epitopes Of The Sars-Cov-2 Spike Protein: Exploring The Intersection Of Binding, Allostery, And Immune Escape With A Multimodal Computational Approach, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Understanding the atomistic basis of multi-layer mechanisms employed by broadly reactive neutralizing antibodies of the SARS-CoV-2 spike protein without directly blocking receptor engagement remains an important challenge in coronavirus immunology. Class 4 antibodies represent an intriguing case: they target a deeply conserved, cryptic epitope on the receptor-binding domain yet exhibit variable neutralization potency across subgroups F1 (CR3022, EY6A, COVA1-16), F2 (DH1047), and F3 (S2X259). The molecular basis for this variability is not fully understood. Here, we employed a multi-modal computational approach integrating atomistic and coarse-grained molecular dynamics simulations, binding free energy calculations, mutational scanning, and dynamic network analysis to elucidate …

Bard1: A Friend Or Foe In Pancreatic Ductal Adenocarcinoma?, Lily Zekavat, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with poor overall prognosis and limited response to standard treatments. Growing interest in the modulation of DNA repair mechanisms, including the homologous recombination (HR) repair pathway, has opened new avenues for therapeutic development. BARD1 (BRCA1-Associated RING Domain 1) plays a complex role in tumor biology, functioning either as a tumor suppressor or as an oncogenic driver, depending on isoform expression, cellular context, and regulatory environment. In this review, we examine the dual roles of BARD1, focusing on its regulation and paradoxical activities in PDAC. We summarize evidence that BARD1 and BARD1 …

Opposing Synovial Cannabinoid Receptor Type 2 And Transient Receptor Potential Vanilloid 1 Expression In Painful Osteoarthritis, Collin A. Toups, Lauren G. Guillot, Kaitlyn Redondo, Sydney Jensen, Jennifer Klein, Luis Marrero

School of Medicine Faculty Publications

Knee osteoarthritis (kOA) poses a major health challenge worldwide, but current non-surgical treatments have limited long-term success and do not address the underlying disease process. This study explores the complex relationship between the endocannabinoid system (ECS) and the endovanilloid system (EVS) in the synovial membrane of patients with kOA undergoing total knee replacement, focusing on how these systems relate to patient-reported pain and histological synovitis. Synovial tissues and fluid from patients grouped into high and low pain categories based on the Knee Injury and Osteoarthritis Outcome Score (KOOS) were examined for cannabinoid receptor type 2 (CB2R), transient receptor potential vanilloid …

Targeting Kinin B1r Attenuates Hypertension Through At1r-Dependent Mechanisms, Drew Theobald, Riley N. Bessetti, Yumei Feng Earley, Eric Lazartigues, Karen Litwa, Srinivas Sriramula

School of Medicine Faculty Publications

BACKGROUND: Neurogenic hypertension is chronically high blood pressure that is initiated and maintained through excessive sympathetic nervous system activity and has been associated with increased B1R (kinin B1 receptor) activation. We previously reported a central role for B1R in mediating inflammatory pathways in the development of deoxycorticosterone acetate salt hypertension. Additionally, we identified a causal relationship between B1R expression after Ang II (angiotensin II) stimulation, and that B1R can mediate the bidirectional interaction between neuroinflammation and oxidative stress. However, whether there are any interactions between AT1R (Ang II-type I receptor) and B1R, and if B1R can mediate the effects of …

Distinct Transcriptional Regulation Of The Wnt And Tgfβ Signaling Families Associated With Wound Healing And Fibrotic Outcomes To Lens Injury, Catherine Lalman, Kylie R. Stabler, Joshua Disatham, Lisa A. Brennan, Marc Kantorow, Janice L. Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Posterior capsule opacification (PCO) is a fibrotic complication of cataract surgery caused by aberrant repair of residual lens cells. It remains unclear how the lens injury response shifts toward a pathological repair process. Here, we performed a transcriptional analysis of two major pro-fibrotic pathways, the TGF-β superfamily and Wnt signaling pathways to determine how they are differentially regulated during regenerative wound healing versus fibrosis in a lens injury model. For these studies, RNA sequencing was performed on an ex vivo lens explant system that models post-surgical healing within regenerative and fibrotic microenvironments, from 0 to 3 days post-injury. Fibrotic conditions …

Resolution Of Physics And Deep Learning-Based Protein Engineering Filters: A Case Study With A Lipase For Industrial Substrate Hydrolysis, Spencer Gardiner, Peter Dollinger, Filip Kovacic, Jörge Pietruszka, Daniel Ess, Karl-Erich Jaeger, Gunnar F. Schröder, Dennis Della Corte

Faculty Publications

Computational enzyme design remains a powerful yet imperfect tool for optimizing biocatalysts, especially when targeting non-natural substrates. Using design tools we investigated Pseudomonas aeruginosa LipA, a lipase with a flexible lid domain crucial for substrate binding and turnover, aiming to enhance its hydrolysis of the industrially relevant substrate Roche ester. We generated an initial set of single-point mutations based on structural proximity to the active site and evaluated their effects using a computational pipeline integrating molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and ensemble-based energy scoring. While we identified several active variants, attempts to rank them by activity …

Air Pollution And Diseases: Signaling, G Protein-Coupled And Toll Like Receptors, Isabella Cattani-Cavalieri, Katrina F. Ostrom, Jordyn Margolis, Rennolds S. Ostrom, Martina Schmidt

Pharmacy Faculty Articles and Research

Air pollution is a significant public health issue that impacts lung health, particularly in vulnerable populations such as children, the elderly, and individuals with pre-existing respiratory conditions. Both natural and anthropogenic sources of air pollution give rise to a variety of toxic compounds, including particulate matter (PM), ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAHs). Exposure to these pollutants is strongly associated with the development and exacerbation of respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). Notably, early life exposure to pollutants such as …

Biofluid Biomarkers Aid In Diagnosing And Developing Improved Treatments For People With Alzheimer's Disease, Jonatan A. Lopez

University Honors Theses

Dementia is a disease in which daily life is disrupted by a loss of cognitive function. Late-onset Alzheimer's disease (AD) is the most common dementia that largely begins to affect individuals in their mid 60s or older. AD was selected as the focus of this paper because it is the most common form of dementia, accounting for 50-70% of dementia cases. A typical diagnostic approach used by physicians starts with a simple clinical test, the Mini-Mental State Examination (MMSE), when cognitive decline is suspected in a patient. Then if there is enough evidence to suggest AD, a physician would order …

Investigating Extracellualr Vesicles Role In The Pathogenesis Of Acute Lung Injury, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Tierney Day, Anca Dobrian, John D. Catravas

Cardiovascular Research Symposium

Background: Extracellular vesicles (EVs) are small lipid-bound particles containing proteins and RNAs, whose role in intercellular communication and signaling is critical for homeostasis or inflammatory responses. Patients with acute lung injury display changes in EVs number, cargo content and signature compared to healthy individuals.

Hypothesis: We have hypothesized that EVs may play a role in the pathogenesis of acute lung, by transferring harmful mediators of inflammation and disrupting recipient cells homeostasis.

Methods: C57BL/6j mice (8-10 weeks old, 25g BW) were intratracheally instilled with 50µL of 5*1010- 11 EVs isolated from Human Lung Microvascular Endothelial cells (HLMVEC) exposed to 1 µg …

Peptide-Based Inorganic Nanoparticles As Efficient Intracellular Delivery Systems, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Anthony Nguyen, Vian Khoury, Keykavous Parang

Pharmacy Faculty Articles and Research

Background/Objectives: Peptide-based inorganic nanoparticles (PINPs) have emerged as promising candidates for intracellular delivery due to their unique structural and functional attributes. These hybrid nanostructures combine the high surface area and tunable optical/magnetic properties of metal cores (e.g., Au, Ag, Fe3O4) with the biocompatibility, targeting specificity, and responsive behavior of peptides. In particular, peptides with amphipathic or cell-penetrating features could facilitate efficient transport of molecular cargos across cellular membranes while enabling stimulus-responsive drug release in target tissues. Methods: We review key synthesis methods (especially green, peptide-mediated one-pot approaches), functionalization strategies (e.g., thiol-gold bonds, click chemistries), and characterization techniques (TEM, …

Interleukin-22 And Interleukin-22 Binding Protein Signaling Axis Influences Intubation Status In Trauma, Augustus E. Anderson, Jacob Broome, Aaron L. Albuck, Megan Shenk, Valeria Noguera, Wid Covey, Alison Smith, Juan Duchesne, Danielle Tatum, Christine M. Bojanowski, Derek Pociask, Jay K. Kolls, Olan Jackson-Weaver, Sharven Taghavi

School of Medicine Faculty Publications

Background: Interleukin-22 is a cytokine involved in mucosal immunity, whereas interleukin-22 binding protein is a soluble receptor that can potently block interleukin-22. The role of interleukin-22 and interleukin-22 binding protein in trauma remains unclear. This study investigates whether IL-22 levels are associated with intubation in patients with trauma. We hypothesized interleukin-22 levels would be lower in intubated patients. Methods: Plasma samples were prospectively obtained in the trauma bay at consecutive Level 1 activations from November 2021 to November 2022. Patients were categorized as having respiratory failure (intubated) or as controls (nonintubated). Two-to-one case-control matching was conducted based on age, sex, …

Silvestrol Inhibits Nasopharyngeal Carcinoma Cells And Synergizes With Cx‑5461: Insights From A Proteomics Study, Maelinda Daker, Munirah Ahmad, Alan Khoo, Lu Ping Tan, Siok-Fong Chin, Siaw San Hwang, Paul Neilsen

Department of Medical Oncology Faculty Papers

Nasopharyngeal carcinoma (NPC) is a cancer arising from the epithelial cells of the nasopharynx, which is rare in Western countries but extremely prevalent in Borneo and the Southern China region. Present-day hurdles in NPC treatment that lead to poor quality of life and poor survival include distant metastasis and resistance to chemoradiotherapy. Silvestrol and its 5'''-epimer, episilvestrol, are compounds isolated from the plant Aglaia stellatopilosa, which is endemic to Borneo. Silvestrol, a protein synthesis inhibitor, preferentially inhibits the translation of cancer-associated mRNAs. CX-5461 is an inhibitor of RNA polymerase I that catalyzes rRNA synthesis. The present study sought to …

Dietary Protein’S Effect On The Gut Microbiome And Its Metabolites: Protocol Description And Virtual Recruitment Efforts For A Remote Randomized Controlled Trial, Karyn M. Gallivan, Kristin S. Ondrak, Denise M. Danos, Meng Luo, Christopher M. Taylor, Lauren E. Meyer, Ann M. Byerley, Alexander W. Nguyen, Sabyasachi Chatterjee, Jiri Adamec, Lauri O. Byerley

School of Medicine Faculty Publications

Fiber’s effect on our gut microbes has been studied extensively, while knowledge of the effect of protein is sparse. Colonic putrefaction of dietary protein is known to produce several potentially detrimental compounds. This randomized controlled trial (RCT) uses a pre- and post-study design to investigate the effect of consuming higher levels of dietary protein on the gut microbiota and the metabolites it produces. Here, we describe our virtual recruitment efforts and RCT protocol. Potential participants lived throughout the contiguous US. Several recruitment methods were employed, of which email reached the largest group of people (approximately 9,100) and generated a 0.3% …

Dynamic Mutational Profiling Of Binding Interactions And Allosteric Networks In Conformational Ensembles Of The Sars-Cov-2 Spike Protein Complexes With Classes Of Antibodies Targeting Cryptic Binding Sites: Confluence Of Binding And Allostery Determines Molecular Mechanisms And Hotspots Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could underlie complexity of broad and escape-resistant neutralization. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how Class 4 antibodies (represented by S2X35, 25F9, and SA55) and Class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the …

Upregulating Ankhd1 In Ps19 Mice Reduces Tau Phosphorylation And Mitigates Tau Toxicity-Induced Cognitive Deficits, Xiaolin Tian, Nathan Le, Yuhai Zhao, Dina Alawamleh, Andrew Schwartz, Lauren Meyer, Elizabeth Helm, Chunlai Wu

School of Graduate Studies Faculty Publications

Using the fly eye as a model system, we previously demonstrated that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration. Building upon this finding, we investigated whether the protective role of mask is conserved in mammals. To this end, we generated a transgenic mouse line carrying Cre-inducible ANKHD1, the human homolog of mask. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we found that expressing ANKHD1 driven by CamK2a-Cre reduced hyperphosphorylated human Tau in 6-month-old mice. Additionally, ANKHD1 expression was associated with a trend toward reduced gliosis and preservation of the presynaptic marker Synaptophysin, suggesting …

Impact Of Cysteine And Tyrosine Dipeptides On Cho Cell Performance In A Perfusion Mimic, Corrin L. Pruitt

All Theses

Perfusion cell cultures typically achieve higher cell densities and generate higher volumetric productivities than fed-batch cultures due to continuous nutrient supply and spent media removal. Despite these advantages, perfusion cell cultures remain underutilized for licensed product manufacturing, primarily due to the lack of small-scale perfusion models for high-throughput process development and the complexities involved in media formulation capable of supporting high cell densities during long-term continuous operation. To avoid nutrient limitation at high cell densities, current perfusion processes rely on using higher perfusion rates, which results in significant media wastage and downstream product dilution. Therefore, there has been an effort …

Cbl Regulation Of C-Met Signaling In Corneal Epithelial Cells., Kate Elise Tarvestad Laise

Electronic Theses and Dissertations

The cornea is the most anterior portion of the eye and permits light passage through to retina, allowing formation of a clear image as long as it remains healthy. If the cornea sustains damage, it creates and entrance for foreign body invasion, infection, and ultimately blindness in the immunocompromised eye. Healing the corneal tissue is critical for vision restoration and pain alleviation, as it is the most densely innervated tissue in the body. Growth factors and their cognate receptors are currently under investigation as tools to restore proper corneal physiology. We hypothesize that manipulating the hepatocyte growth factor (HGF) /c-Met …

Ctnna3 Deficiency Promotes Heart Regeneration By Enhancing Cardiomyocyte Proliferation In Neonatal Mice, Sha Zou, Wuhou Dai, Wufan Tao, Jifen Li, Zeyi Cheng, Hongyan Wang

Department of Medicine Faculty Papers

Background: Heart regeneration requires renewal of lost cardiomyocytes. However, the mammalian heart loses its proliferative capacity soon after birth, and the molecular signaling underlying the loss of cardiac proliferation postnatally is not fully understood.

Purpose: This study aimed to investigate the role of Catenin alpha 3 (Ctnna3), coding for alpha T catenin (αT-catenin) protein in regulating cardiomyocyte proliferation and heart regeneration during the neonatal period.

Methods: Here we report that ablation of Ctnna3 and highly expressed in hearts, accelerated heart regeneration following heart apex resection in neonatal mice.

Results: Our results show that Ctnna3 deficiency enhances cardiomyocyte proliferation …

Effects Of Liver Surgery On Drug Transporters In The Liver And Remote Organs, Reza Mehvar

Pharmacy Faculty Articles and Research

Alterations in drug transporters in acute liver failure and chronic liver diseases, such as cirrhosis, have been reviewed before. However, there is a lack of comprehensive reviews on how liver surgery, including transplantation and partial hepatectomy, affects drug transporters. Because ischemia–reperfusion (IR) injury is a hallmark of liver transplantation and most other surgical procedures of the liver, this review focuses on the effects of IR injury, in addition to liver resection, on the expression and function of transporters in the liver and remote organs. Most of the reported studies in this area are carried out in animal models of liver …

A Mutational Analysis Of Thatisin: How Single Point Mutations Impact The Biosynthetic Process Of A Group 16 Graspetide, John F. Boynton Jr

Chemistry and Chemical Biology ETDs

Abstract:

Graspetides are a family of Ribosomally synthesized and Post-translationally modified Peptide (RiPP) natural products named for their ATP Grasp Macrocyclases. We identified several Graspetide Biosynthetic Gene Clusters containing common double glycine cleavage motifs and attempted characterization of the mature Graspetides. One of the resulting peptides, Thatisin, has a topology with two interlocking macrolactones installed by a single ATP Grasp Ligase named ThtC. Here we use single and double point mutations to observe the impact or variation on the installation of these macrocycles. Alanine scan mutagenesis is used to assess leader peptide residues in the precursor peptide ThtA to determine …

Multiscale Modeling And Dynamic Mutational Profiling Of Binding Energetics And Immune Escape For Class I Antibodies With Sars-Cov-2 Spike Protein: Dissecting Mechanisms Of High Resistance To Viral Escape Against Emerging Variants, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibodies—BD55-1205, BD-604, OMI-42, P5S-1H1, and P5S-2B10—and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using multiscale modeling, which combined molecular simulations with the ensemble-based mutational scanning of the binding interfaces and binding free energy computations. A central theme emerging from this work is that the unique binding strength and resilience to immune escape of the BD55-1205 antibody are determined by leveraging a broad epitope …

Templating Of Monomeric Alpha-Synuclein Results In Inflammation And Snpc Dopamine Neuron Death In A Genetic Mouse Model Of Induced Synucleinopathy, Matthew D. Byrne, Peyman Petramfar, Jae-Kyung Lee, Richard J. Smeyne

Department of Neuroscience Faculty Papers

While the etiology of most cases of Parkinson's disease (PD) are idiopathic, it has been estimated that 5-10% of PD arise from known genetic mutations. The first mutations described that leads to the development of an autosomal dominant form of PD are in the SNCA gene that codes for the protein alpha-synuclein (α-syn). α-syn is an abundant presynaptic protein that is natively disordered and whose function is still unclear. In PD, α-syn misfolds into multimeric b-pleated sheets that aggregate in neurons (Lewy Bodies/neurites) and spread throughout the neuraxis in a pattern that aligns with disease progression. Here, using IHC, HC, …

First-In-Human Phase I Open-Label Study Of The Anti-Tim-3 Monoclonal Antibody Incagn02390 In Patients With Select Advanced Or Metastatic Solid Tumors, Martin E. Gutierrez, Shou Ching Tang, John D. Powderly, Ani S. Balmanoukian, Paul E. Hoyle, Zhiwan Dong, Lulu Cheng, Xiaohua Gong, John E. Janik, Nawel Bourayou, Omid Hamid

School of Medicine Faculty Publications

Background T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is an immune checkpoint receptor upregulated during anti-programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy for cancer. TIM-3 blockade may improve the antitumor activity of PD-1/PD-L1inhibition. This phase 1 study evaluated INCAGN02390, a novel, fully human Fc-engineered antibody against TIM-3. Methods INCAGN02390 was evaluated by dose escalation at 10-1600 mg infused in 14-day cycles (every 2 weeks [Q2W]) in pretreated patients with select advanced/metastatic immunogenic solid tumors. Objectives included evaluation of safety/tolerability and maximum tolerated dose (MTD) (primary), pharmacokinetics, preliminary antitumor activity, pharmacodynamics, and immunogenicity (secondary). Results Forty patients were enrolled and …

Modulation Of Redox-Sensitive Cardiac Ion Channels, Rawan S. Orfali, Al Hassan Gamal El-Din, Varnika Karthik, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate …

Kshv Vil6 Inhibits Functional B Cell Maturation During De Novo Infection, Wajd Zakir, Jessica M. Osborn, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Despite causative links to lymphoproliferative disorders, little is known about early events governing KSHV infection in B lymphocytes. IL-6 signaling plays a critical role in KSHV-mediated disease, with human IL-6 (hIL6) levels correlating with viral load and disease progression. This dynamic is even more complex due to the coexistence of hIL6 and KSHV-encoded viral IL-6 (vIL6) in these diseases. We hypothesize that hIL6 and vIL6 play critical, separable and collective roles in the early stages of KSHV infection in B cells. In this study, we use our ex vivo model of KSHV infection in human tonsil lymphocytes to investigate the …

New Onset Diabetic Retinopathy With Glucagon-Like Peptide-1 Receptor Agonists: A Case Report, Jennifer Ko, Yaseman Jahromi

Pharmacy Faculty Articles and Research

Background

Surface Keratin 1, A Tumor-Selective Peptide Target In Human Triple-Negative Breast Cancer, Shih-Jing Yao, Farideh Amirrad, Elmira Ziaei, Azam Saghaeidehkordi, Moom R. Roosan, Kiumars Shamloo, Ajay Sharma, Rachita K. Sumbria, Surya M. Nauli, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Targeting drugs to cancer cells via overexpressed cell-surface receptors has emerged as an effective therapeutic strategy for several cancers. However, identifying cell-surface receptors that allow selective uptake of targeting ligands by cancer cells—while sparing normal cells—remains a challenge, especially for triple-negative breast cancer (TNBC), which lacks a well-defined receptor for targeted delivery. In this study, immunohistochemical (IHC) analysis revealed that human TNBC patient tissues have significantly higher levels of keratin 1 (K1) compared to normal breast tissues. Among TNBC tissues, grade 3 tumors showed significantly higher (threefold) K1 expression compared to grade 2 tumors. We analyzed human TNBC and normal …

Ifi16 Mediates Deacetylation Of Kshv Chromatin Via Interaction With Nurd And Sin3a Co-Repressor Complexes, Anandita Ghosh, Bala Chandran, Arunava Roy

School of Medicine Faculty Publications

IFI16 is a well-characterized nuclear innate immune DNA sensor that detects foreign dsDNA, including herpesviral genomes, to activate the inflammasome and interferon pathways. Beyond immune signaling, IFI16 also functions as an antiviral restriction factor, promoting the silencing of invading viral genes through transcriptional and epigenetic mechanisms. We recently demonstrated another role of IFI16, in which it interacts with and recruits the class I histone deacetylases, HDAC1 and 2, to the KSHV latency protein LANA, modulating its acetylation and function. In this study, we asked whether these IFI16-HDAC1/2 interactions contribute to broader epigenetic regulation of the KSHV chromatin. Our findings reveal …

Impact Of Stereochemical Replacement On Activity And Selectivity Of Membrane-Active Antibacterial And Antifungal Cyclic Peptides, Sandeep Lohan, Anastasia G. Konshina, Eman H. M. Mohammed, Naiera M. Helmy, Srishhti K. Jha, Rakesh Kumar Tiwari, Innokentiy Maslennikov, Roman G. Efremov, Keykavous Parang

Pharmacy Faculty Articles and Research

Herein, we report a library of 7-mer macrocyclic peptides designed by systematically replacing one, multiple, or all L-amino acids with their D-isomers in our previously identified hit compounds. Lead peptides, 15c and 16c, showed broad-spectrum activity against bacteria (Gram-positive minimum inhibitory activity (MIC 1.5–6.2 µg/mL and Gram-negative MIC 6.2–25 µg/mL) and fungi (MIC = 3.1–25 µg/mL). Additionally, peptides 15c and 16c showed rapid kill kinetics and biofilm degradation potential against both bacteria and fungi, while resistance development was not observed. The antimicrobial effect of these macrocyclic peptides was attributed to their membranolytic action, which was confirmed by calcein dye …

Abstract 2587 Recombinant Expression And Purification Of A. Vinelandii Cown In E. Coli, Julie Takei, Cedric P. Owens, Katie Sanders, Neeraja Gajendran

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The goal of this project is to study the protein CowN in the diazotroph Azotobacter vinelandii (Av) in comparison to CowN in Gluconacetobacter diazotrophicus (Gd). Nitrogenase is an enzyme that catalyzes the reduction of nitrogen gas into ammonia in diazotrophic bacteria. In many diazotrophs, the protein CowN prevents nitrogenase inhibition from the environmental gas carbon monoxide (CO). Previous work studied CowN in the diazotroph G. diazotrophicus. In G. diazotrophicus, CowN binds to nitrogenase and weakens CO binding to its active site. The mechanism of CowN has only been investigated in G. diazotrophicus. Thus, we are interested in determining if CowN's …