Chemistry Commons^™

Potency And Properties Of Hydrazide Compounds That Inhibit The Growth Of Mycobacterium Tuberculosis, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To examine the properties of hydrazide compounds shown to inhibit Mycobacterium tuberculosis. To identify properties that affect efficiency of bacterial inhibition.

Study Design: Utilizing data from previous studies of compounds that inhibit Mycobacterium tuberculosis, then statistical and pattern recognition methods are applied to identify interrelationships.

Place and Duration of Study: Department of Chemistry, Durham Science Center, University of Nebraska at Omaha, from January 2016 to July 2016.

Methodology: Interrelationships of pharmacological properties were identified by use of various pattern recognition techniques, such as hierarchical cluster analysis and path analysis. Molecular properties and descriptors for all compounds were …

Myofilament Calcium Sensitivity: Consequences Of The Effective Concentration Of Troponin I, Jalal K. Siddiqui, Svetlana B. Tikunova, Shane D. Walton, Bin Liu, Meredith Meyer, Pieter P. De Tombe, Nathan Neilson, Peter M. Kekenes-Huskey, Hussam E. Salhi, Paul M.L. Janssen, Brandon J. Biesiadecki, Jonathan P. Davis

Chemistry Faculty Publications

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to …

Electropolymerization Of B–Cyclodextrin Onto Multi–Walled Carbon Nanotube Composite Films For Enhanced Selective Detection Of Uric Acid, Mulugeta B. Wayu, Luke T. Dipasquale, Margaret A. Schwarzmann, Samuel D. Gillespie, Michael C. Leopold

Chemistry Faculty Publications

An amperometric uric acid (UA) sensor incorporating a multi-walled carbon nanotubes (MWCNT) network in Nafion and electropolymerized β-cyclodextrin (β-CD) layer is investigated. The electrochemical sensor is comprised of a glassy carbon electrode modified with Nafion-MWCNT nanocomposite film, a β-CD polymer inner selective layer, and a Hydrothane polyurethane (HPU) outer selective coating. The surface morphology and electronic structure of the electrode material are characterized using transmission electron microscopy (TEM), scanning electron microscope (SEM), and Fourier transform infrared (FTIR) spectroscopy. The electrocatalytic activity of the sensor is studied using cyclic voltammetry (CV), chronocoulometry (CC) and differential pulse voltammetry (DPV). Analytical performance of …

Secondary Structure Adopted By The Gly-Gly-X Repetitive Regions Of Dragline Spider Silk, Geoffrey M Gray, Arjan Van Der Vaart, Chengchen Guo, Justin Jones, David Onofrei, Brian R Cherry, Randolph V Lewis, Jeffery L Yarger, Gregory P Holland

Chemistry Faculty Publications

Solid-state NMR and molecular dynamics (MD) simulations are presented to help elucidate the molecular secondary structure of poly(Gly-Gly-X), which is one of the most common structural repetitive motifs found in orb-weaving dragline spider silk proteins. The combination of NMR and computational experiments provides insight into the molecular secondary structure of poly(Gly-Gly-X) segments and provides further support that these regions are disordered and primarily non-β-sheet. Furthermore, the combination of NMR and MD simulations illustrate the possibility for several secondary structural elements in the poly(Gly-Gly-X) regions of dragline silks, including β-turns, 3

Subtractive Methods To Form Pyrite And Sulfide Nanostructures Of Fe, Co, Ni, Cu And Zn, Kurt W. Kolasinski

Chemistry Faculty Publications

The low Z metals Fe, Co, Ni, Cu and Zn are Earth abundant, i.e. inexpensive, and their sulfides are of low toxicity. This makes them appealing candidates for materials applications requiring semiconductors or, in the case of CoS₂, a metal since they can potentially be produced in large quantities and low cost. Though of great potential little work has explored how subtractive methods can be used to form nanostructured and/or porous structures in, e.g. FeS₂, CoS₂, NiS, Cu₂S and ZnS.

Glutathione Species And Metabolomic Prints In Subjects With Liver Disease As Biological Markers For The Detection Of Hepatocellular Carcinoma, Juan R. Sanabria, Rajan S. Kombu, Guo Fang Zhang, Yana Sandlers, Jizhou Ai, Rafael A. Ibarra, Rime Abbas, Kush Goyal, Henri Brunengraber

Chemistry Faculty Publications

© 2016 The Authors Background The incidence of liver disease is increasing in USA. Animal models had shown glutathione species in plasma reflects liver glutathione state and it could be a surrogate for the detection of hepatocellular carcinoma (HCC). Methods The present study aimed to translate methods to the human and to explore the role of glutathione/metabolic prints in the progression of liver dysfunction and in the detection of HCC. Treated plasma from healthy subjects (n = 20), patients with liver disease (ESLD, n = 99) and patients after transplantation (LTx, n = 7) were analyzed by GC- or LC/MS. …

Spray Printing Of Organic Semiconducting Single Crystals, Grigorios-Panagiotis Rigas, Marcia M. Payne, John E. Anthony, Peter N. Horton, Fernando A. Castro, Maxim Shkunov

Chemistry Faculty Publications

Single-crystal semiconductors have been at the forefront of scientific interest for more than 70 years, serving as the backbone of electronic devices. Inorganic single crystals are typically grown from a melt using time-consuming and energy-intensive processes. Organic semiconductor single crystals, however, can be grown using solution-based methods at room temperature in air, opening up the possibility of large-scale production of inexpensive electronics targeting applications ranging from field-effect transistors and light-emitting diodes to medical X-ray detectors. Here we demonstrate a low-cost, scalable spray-printing process to fabricate high-quality organic single crystals, based on various semiconducting small molecules on virtually any substrate by …

Giant Electrorheological Fluids With Ultrahigh Electrorheological Efficiency Based On A Micro/Nano Hybrid Calcium Titanyl Oxalate Composite, Jinghua Wu, Zhenyang Song, Fenghua Liu, Jianjun Guo, Yuchuan Cheng, Shengqian Ma, Gaojie Xu

Chemistry Faculty Publications

A novel micro/nanoparticle hybrid calcium titanyl oxalate electrorheological (ER) material composed of micron-sized spindly particles and nanometer-sized irregular particles was successfully fabricated. The giant ER fluid based on the composite exhibits enhanced not only yield stress but also low field-off viscosity, thereby resulting in an ultrahigh ER efficiency that greatly exceeds that of any existing giant ER (GER) material. The synergistic effect between the spindly microparticles and irregular nanoparticles discovered in this study suggests a promising method for solving the long-standing ER efficiency problems. Moreover, the one-step synthesis approach presented in this work can be readily expanded for mass production …

Towards An Understanding Of The Propensity For Crystalline Hydrate Formation By Molecular Compounds, Alankriti Bajpai, Hayley S Scott, Tony Pham, Kai-Jie Chen, Brian Space, Matteo Lusi, Miranda L Perry, Michael J Zaworotko

Chemistry Faculty Publications

Hydrates are technologically important and ubiquitous yet they remain a poorly understood and understudied class of molecular crystals. In this work, we attempt to rationalize propensity towards hydrate formation through crystallization studies of molecules that lack strong hydrogen-bond donor groups. A Cambridge Structural Database (CSD) survey indicates that the statistical occurrence of hydrates in 124 molecules that contain five- and six-membered N-heterocyclic aromatic moieties is 18.5%. However, hydrate screening experiments on a library of 11 N-heterocyclic aromatic compounds with at least two acceptor moieties and no competing hydrogen-bond donors or acceptors reveals that over 70% of this group …

Imparting Amphiphobicity On Single-Crystalline Porous Materials., Qi Sun, Hongming He, Wen-Yang Gao, Briana Aguila, Lukasz Wojtas, Zhifeng Dai, Jixue Li, Yu-Sheng Chen, Feng-Shou Xiao, Shengqian Ma

Chemistry Faculty Publications

The sophisticated control of surface wettability for target-specific applications has attracted widespread interest for use in a plethora of applications. Despite the recent advances in modification of non-porous materials, surface wettability control of porous materials, particularly single crystalline, remains undeveloped. Here we contribute a general method to impart amphiphobicity on single-crystalline porous materials as demonstrated by chemically coating the exterior of metal-organic framework (MOF) crystals with an amphiphobic surface. As amphiphobic porous materials, the resultant MOF crystals exhibit both superhydrophobicity and oleophobicity in addition to retaining high crystallinity and intact porosity. The chemical shielding effect resulting from the amphiphobicity of …

The Tribology And Chemistry Of Phosphorus Containing Lubricant Additives, David W. Johnson

Chemistry Faculty Publications

Phosphate esters, thiophosphate esters and metal thiophosphates have been used as lubricant additives for over 50 years. Recently, phosphorus‐containing ionic liquids have emerged as a new class of lubricant additives. While the use of phosphorus compounds has been extensive, a detailed knowledge of how they work has been a much more recent development. In this chapter, the use of phosphate esters, thiophosphate esters, metal thiophosphates and phosphorus‐containing ionic liquids as antiwear or extreme pressure additives is discussed. The primary emphasis will be on how they form a protective film, which is both durable and reduces friction. The first part of …

Water Quality In And Around Glen Helen Nature Preserve Fall 2016, Krista Baumgartner, Kellie Bohrer, Brandon Bresler, Thomas Chenault, Miriam Crane, Jennifer Dean, James Herbort, Kelsey Hood, Megan Shade, Kraig Strayer, Nicholas Yahana, Emily Warren, Ben Silliman, Brandon Myers, Steven Ujvary, Audrey E. Mcgowin

Chemistry Faculty Publications

No abstract provided.

Chemotherapeutic Agents From Natural Product Templates: The Design And Synthesis Of Novel Indanone Analogues, Mark F. Mechelke, Sarah Hopfner, Natalie Mcintire, Nathanial Cherry

Chemistry Faculty Publications

Coumarin is a natural product found in many plants. Recently, simple coumarin analogues containing an α-methylene functional group have been synthesized and shown to exhibit cytotoxicity against cancer cell lines. The α,β-unsaturated carbonyl found in these analogues is thought to be responsible for their bioactivity. Other natural products containing this functional group have been shown to react with intracellular thiols causing tumor growth suppression. Using these analogues as a template, two new compounds have been designed that feature a novel α-methylene indanone structural framework. Since ketones are better electrophiles that esters, it is hypothesized that these analogues will react more …

Chemotherapeutic Drug Design: An Efficient Synthesis Of 4-Substituted Alpha-Methylene-Gamma-Lactones, Mark F. Mechelke, Katy Platt, Connor Pribula

Chemistry Faculty Publications

Sesquiterpene lactones are plant-derived compounds that have been shown to possess significant activity against inflammation and cancer. Comparative studies of sesquiterpene lactone structure and tumor cytotoxicity indicate that the presence of an α-methylene-γ-lactone moiety is necessary for bioactivity. This observation has led to the hypothesis that simple compounds containing this pharmacophore may also exhibit similar anti-cancer properties. To test this theory, an efficient synthesis of 4-substituted α-methylene-γ-lactone has been developed. The model compound in this study, α-methylene-γ-dodecalactone, has been prepared from commercially available 1-decene in six steps. The synthesis features a nucleophilic epoxide ring-opening reaction followed by an intramolecular cyclization …

Responding To The U.S. Research Community's Liquid Helium Crisis, Simon R. Bare, Michael Lilly, Janie Chermak, Rod Eggert, William Halperin, Scott Hannahs, Sophia Hayes, Michael Hendrich, Alan Hurd, Mike Osofsky, Cathy Tway

Chemistry Faculty Publications

An Action Plan to Preserve U.S. Innovation. This report lays out the issues facing researchers who use liquid helium and the negative impact on U.S. innovation. The report then proposes five key steps that will have a transformative effect on the ability to maintain the ready availability of helium and ensure the vibrancy of the U.S. low-temperature research capability. These recommendations focus on: conservation of helium use; a mechanism to pay for the capital investment required for helium recycling; a mechanism to ensure an appropriate price is paid by researchers for helium; and a methodology which allows researchers to best …

Grain Boundary Induced Bias Instability In Soluble Acene-Based Thin-Film Transistors, Ky V. Nguyen, Marcia M. Payne, John E. Anthony, Jung Hun Lee, Eunjoo Song, Boseok Kang, Kilwon Cho, Wi Hyoung Lee

Chemistry Faculty Publications

Since the grain boundaries (GBs) within the semiconductor layer of organic field-effect transistors (OFETs) have a strong influence on device performance, a substantial number of studies have been devoted to controlling the crystallization characteristics of organic semiconductors. We studied the intrinsic effects of GBs within 5,11-bis(triethylsilylethynyl) anthradithiophene (TES-ADT) thin films on the electrical properties of OFETs. The GB density was easily changed by controlling nulceation event in TES-ADT thin films. When the mixing time was increased, the number of aggregates in as-spun TES-ADT thin films were increased and subsequent exposure of the films to 1,2-dichloroethane vapor led to a significant …

Lubricants For Turbine Engines, David W. Johnson

Chemistry Faculty Publications

The lubricant systems used in turbine engine applications are discussed with respect to the particular problems associated with aircraft applications. After initially describing the relevant specifications, the typical basestocks are described along with some common degradation schemes. The additive systems, including antioxidants, anti-foaming agents, and anti-wear additives needed to achieve the typical specifications, are described along with their mechanism of action and degradation mechanisms. The methods used for the monitoring of lubricant health, including in-line and offline methods, are also discussed. Finally, future changes in specifications, basestocks, and additives are discussed with respect to new, high-performance bearing materials.

Relating Side Chain Organization Of Pnipam With Its Conformation In Aqueous Methanol, Debashish Mukherji, Manfred Wagner, Mark D. Watson, Svenja Winzen, Tiago E. E. De Oliveira, Carlos M. Marques, Kurt Kremer

Chemistry Faculty Publications

Combining nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and μs long all-atom simulations with two million particles, we establish a delicate correlation between increased side chain organization of PNIPAm and its collapse in aqueous methanol mixtures. We find that the preferential binding of methanol with PNIPAm side chains, bridging distal monomers along the polymer backbone, results in increased organization. Furthermore, methanol–PNIPAm preferential binding is dominated by hydrogen bonding. Our findings reveal that the collapse of PNIPAm is dominated by enthalpic interactions and that the standard poor solvent (entropic) effects play no major role.

Nmr Analysis Of T‐Butyl‐Catalyzed Deuterium Exchange At Unactivated Arene Localities, Douglas E. Stack, Rachel Eastman

Chemistry Faculty Publications

Regioselective labelling of arene rings via electrophilic exchange is often dictated by the electronic environment caused by substituents present on the aromatic system. Previously, we observed the presence of a t‐butyl group, either covalently bond or added as an external reagent, could impart deuterium exchange to the unactivated, C1‐position of estrone. Here, we provide nuclear magnetic resonance analysis of this exchange in a solvent system composed of 50:50 trifluoroacetic acid and D2O with either 2‐t‐butylestrone or estrone in the presence of t‐butyl alcohol has shed insights into the mechanism of this t‐butyl‐catalyzed exchange. Fast exchange of the t‐butyl group concurrent …

0+ States In 130,132Xe: A Search For E(5) Behavior, Erin E. Peters, T. J. Ross, S. F. Ashley, Anagha Chakraborty, Benjamin P. Crider, M. D. Hennek, Sinong Liu, Marcus T. Mcellistrem, Sharmistha Mukhopadhyay, Francisco M. Prados-Estévez, Anthony Paul Ramirez, J. S. Thrasher, Steven W. Yates

Chemistry Faculty Publications

The level structures of ^130,132Xe were studied with the inelastic neutron scattering reaction followed by γ-ray detection. Level lifetimes were measured using the Doppler-shift attenuation method and low-lying excited states in these nuclei were characterized. With a focus on the decay properties of the 0⁺ states, these nuclei were examined as representations of the E(5) critical-point symmetry.

Inhibiting Androgen Receptor Nuclear Entry In Castration-Resistant Prostate Cancer, Julie A. Pollock, Suzanne E. Wardell, Alexander A. Parent, David B. Stagg, Stephanie J. Ellison, Holly M. Alley, Christina A. Chao, Scott A. Lawrence, James P. Stice, Ivan Spasojevic, Jennifer G. Baker, Sung Hoon Kim, Donald P. Mcdonnell, John A. Katzenellenbogen, John D. Norris

Chemistry Faculty Publications

Clinical resistance to the second-generation antiandrogen enzalutamide in castration resistant prostate cancer (CRPC), despite persistent androgen receptor (AR) activity in tumors, highlights the unmet medical need for next generation antagonists. We have identified and characterized tetra-aryl cyclobutanes (CBs) as a new class of competitive AR antagonists that exhibit a unique mechanism of action. These CBs are structurally distinct from current antiandrogens (hydroxyflutamide, bicalutamide, and enzalutamide), and inhibit AR-mediated gene expression, cell proliferation, and tumor growth in several models of CRPC. Conformational profiling revealed that CBs stabilize an AR conformation resembling an unliganded receptor. Using a variety of techniques, it was …

Intramolecular 1,5-C(Sp3)–H Radical Amination Via Co(Ii)-Based Metalloradical Catalysis For Five-Membered Cyclic Sulfamides, Hongjian Lu, Kai Lang, Huiling Jiang, Lukasz Wojtas, X Peter Zhang

Chemistry Faculty Publications

Co(II)-based metalloradical catalysis (MRC) proves effective for intramolecular 1,5-C–H amination of sulfamoyl azides under neutral and nonoxidative conditions, providing a straightforward approach to access strained 5-membered cyclic sulfamides with nitrogen gas as the only byproduct. The metalloradical amination system is applicable to different types of C(sp³)–H bonds and has a high degree of functional group tolerance. Additional features of the Co(II)-catalyzed 1,5-C–H amination include excellent chemoselectivity toward allylic and propargylic C–H bonds. The unique reactivity and selectivity profile of the Co(II)-catalyzed 1,5-C–H amination is attributed to the underlying radical mechanism of MRC.

Layered Xerogel Films Incorporating Monolayer Protected Cluster Networks On Platinum Black Modified Electrodes For Enhanced Sensitivity In 1st Generation Uric Acid Biosensing, Mulugeta B. Wayu, Michael J. Pannell, Michael C. Leopold

Chemistry Faculty Publications

Amperometric uric acid (UA) biosensing schemes incorporating networks of alkanethiolate‐protected gold nanoparticles, monolayer protected clusters (MPCs), and platinum black (Pt‐B) electrode modification through the layer‐by‐layer construction of xerogels are investigated. MPC doping and Pt‐B augmentation are implemented within hydroxymethyltriethoxysilane xerogel bilayers at platinum electrodes. The first xerogel adlayer is doped with an MPC network and houses uricase for the enzymatic reaction required for first‐generation schemes. Polyluminol–aniline and polyurethane are used as selective/stabilizing interfacial layers. The sensing performance with and without Pt‐B and/or MPC doping is assessed by amperometry with standardized UA injections. The use of each individual material results in …

Mutation Linked To Autosomal Dominant Nocturnal Frontal Lobe Epilepsy Reduces Low-Sensitivity Α4Β2, And Increases Α5Α4Β2, Nicotinic Receptor Surface Expression, Weston A. Nichols, Brandon J. Henderson, Christopher B. Marotta, Caroline Y. Yu, Chris Richards, Dennis A. Dougherty, Henry A. Lester, Bruce N. Cohen

Chemistry Faculty Publications

A number of mutations in α4β2-containing (α4β2*) nicotinic acetylcholine (ACh) receptors (nAChRs) are linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), including one in the β2 subunit called β2V287L. Two α4β2* subtypes with different subunit stoichiometries and ACh sensitivities co-exist in the brain, a high-sensitivity subtype with (α4)₂(β2)₃ subunit stoichiometry and a low-sensitivity subtype with (α4)₃(β2)₂ stoichiometry. The α5 nicotinic subunit also co-assembles with α4β2 to form a high-sensitivity α5α4β2 nAChR. Previous studies suggest that the β2V287L mutation suppresses low-sensitivity α4β2* nAChR expression in a knock-in mouse model and also that α5 co-expression …

An Experimental And Theoretical Study Of Ã2A"Π–X~2A' Band System Of The Jet-Cooled Hbbr/Dbbr Free Radical, Mohammed Gharaibeh, Dennis J. Clouthier, Riccardo Tarroni

Chemistry Faculty Publications

The electronic spectra of the HBBr and DBBr free radicals have been studied in depth. These species were prepared in a pulsed electric discharge jet using a precursor mixture of BBr₃ vapor and H₂ or D₂ in high pressure argon. Transitions to the electronic excited state of the jet-cooled radicals were probed with laser-induced fluorescence and the ground state energy levels were measured from the single vibronic level emission spectra. HBBr has an extensive band system in the red which involves a linear-bent transition between the two Renner-Teller components of what would be a ²Π state …

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S Mhashilkar, Sai L Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R Palli, H. Lee Woodcock Iii, Thomas R Unnasch

Chemistry Faculty Publications

BACKGROUND: A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

METHODOLOGY/ PRINCIPAL FINDINGS: Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. …

Aqueous Photochemistry Of Glyoxylic Acid, Alexis J. Eugene, Sha-Sha Xia, Marcelo I. Guzman

Chemistry Faculty Publications

Aerosols affect climate change, the energy balance of the atmosphere, and public health due to their variable chemical composition, size, and shape. While the formation of secondary organic aerosols (SOA) from gas phase precursors is relatively well understood, studying aqueous chemical reactions contributing to the total SOA budget is the current focus of major attention. Field measurements have revealed that mono-, di-, and oxo-carboxylic acids are abundant species present in SOA and atmospheric waters. This work explores the fate of one of these 2-oxocarboxylic acids, glyoxylic acid, which can photogenerate reactive species under solar irradiation. Additionally, the dark thermal aging …

Oncogenic Pik3ca Mutations Reprogram Glutamine Metabolism In Colorectal Cancer, Yujun Hao, Yardena Samuels, Qingling Li, Dawid Krokowski, Bo-Jhih Guan, Chao Wang, Zhicheng Jin, Bohan Dong, Bo Cao, Xiujing Feng, Min Xiang, Claire Xu, Stephen Fink, Neal J. Meropol, Yan Xu

Chemistry Faculty Publications

Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to alpha-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110 alpha upregulates GPT2 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not …

Novel Protein Disulfide Isomerase Inhibitor With Anticancer Activity In Multiple Myeloma, Sergei Vatolin, James G. Phillips, Babal K. Jha, Shravya Govindgari, Jennifer Hu, Dale Grabowski, Yvonne Parker, Daniel J. Lindner, Fei Zhong, Clark W. Distelhorst, Mitchell R. Smith, Claudiu Cotta, Yan Xu, Sujatha Chilakala, Rebecca R. Kuang, Samantha Tall, Frederic J. Reu

Chemistry Faculty Publications

Multiple myeloma cells secrete more disulfide bond–rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell–based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrow–sparing compound, exhibited a submicromolar IC₅₀ in 10 of 10 multiple myeloma cell lines. An active biotinylated analog …

Glen Helen Water Quality: A 5-Year Exploration, 2011-2015 (Acs), Audrey E. Mcgowin Ph.D.

Chemistry Faculty Publications

No abstract provided.