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Full-Text Articles in Physical Sciences and Mathematics
Absolute Configuration Of 2,2',3,3',6-Pentachlorinatedbiphenyl (Pcb 84) Atropisomers, Xueshu Li, Sean R. Parkin, Hans-Joachim Lehmler
Absolute Configuration Of 2,2',3,3',6-Pentachlorinatedbiphenyl (Pcb 84) Atropisomers, Xueshu Li, Sean R. Parkin, Hans-Joachim Lehmler
Chemistry Faculty Publications
Nineteen polychlorinated biphenyl (PCB) congeners, such as 2,2′,3,3′,6-pentachlorobiphenyl (PCB 84), display axial chirality because they form stable rotational isomers, or atropisomers, that are non-superimposable mirror images of each other. Although chiral PCBs undergo atropselective biotransformation and atropselectively alter biological processes, the absolute structure of only a few PCB atropisomers has been determined experimentally. To help close this knowledge gap, pure PCB 84 atropisomers were obtained by semi-preparative liquid chromatography with two serially connected Nucleodex β-PM columns. The absolute configuration of both atropisomers was determined by X-ray single-crystal diffraction. The PCB 84 atropisomer eluting first and second on the Nucleodex β-PM …
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
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 …
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
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. …
Molecular Mechanism Of Protein Kinase Recognition And Sorting By The Hsp90 Kinome-Specific Cochaperone Cdc37, Dimitra Keramisanou, Adam Aboalroub, Ziming Zhang, Wenjun Liu, Devon Marshall, Andrea Diviney, Randy W. Larsen, Ralf Landgraf, Ioannis Gelis
Molecular Mechanism Of Protein Kinase Recognition And Sorting By The Hsp90 Kinome-Specific Cochaperone Cdc37, Dimitra Keramisanou, Adam Aboalroub, Ziming Zhang, Wenjun Liu, Devon Marshall, Andrea Diviney, Randy W. Larsen, Ralf Landgraf, Ioannis Gelis
Chemistry Faculty Publications
Despite the essential functions of Hsp90, little is known about the mechanism that controls substrate entry into its chaperone cycle. We show that the role of Cdc37 cochaperone reaches beyond that of an adaptor protein and find that it participates in the selective recruitment of only client kinases. Cdc37 recognizes kinase specificity determinants in both clients and nonclients and acts as a general kinase scanning factor. Kinase sorting within the client-to-nonclient continuum relies on the ability of Cdc37 to challenge the conformational stability of clients by locally unfolding them. This metastable conformational state has high affinity for Cdc37 and forms …
Restricted Mobility Of Specific Functional Groups Reduces Anti-Cancer Drug Activity In Healthy Cells, Murillo L. Martins, Rosanna Ignazzi, Juergen Eckert, Benjamin Watts, Ramon Kaneno, Willian F Zambuzzi, Luke Daemen, Margarida J Saeki, Heloisa N Bordallo
Restricted Mobility Of Specific Functional Groups Reduces Anti-Cancer Drug Activity In Healthy Cells, Murillo L. Martins, Rosanna Ignazzi, Juergen Eckert, Benjamin Watts, Ramon Kaneno, Willian F Zambuzzi, Luke Daemen, Margarida J Saeki, Heloisa N Bordallo
Chemistry Faculty Publications
The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the …
It Is All About (U)Biquitin: Role Of Altered Ubiquitin-Proteasome System And Uchl1 In Alzheimer Disease, Antonella Tramutola, Fabio Di Domenico, Eugenio Barone, Marzia Perluigi, D. Allan Butterfield
It Is All About (U)Biquitin: Role Of Altered Ubiquitin-Proteasome System And Uchl1 In Alzheimer Disease, Antonella Tramutola, Fabio Di Domenico, Eugenio Barone, Marzia Perluigi, D. Allan Butterfield
Chemistry Faculty Publications
Free radical-mediated damage to macromolecules and the resulting oxidative modification of different cellular components are a common feature of aging, and this process becomes much more pronounced in age-associated pathologies, including Alzheimer disease (AD). In particular, proteins are particularly sensitive to oxidative stress-induced damage and these irreversible modifications lead to the alteration of protein structure and function. In order to maintain cell homeostasis, these oxidized/damaged proteins have to be removed in order to prevent their toxic accumulation. It is generally accepted that the age-related accumulation of “aberrant” proteins results from both the increased occurrence of damage and the decreased efficiency …
Inactivation Of Peptidylglycine Α-Hydroxylating Monooxygenase By Cinnamic Acid Analogs, Neil R. Mcintyre, Edward W. Lowe Jr, Matthew R. Battistini, James W. Leahy, David J. Merkler
Inactivation Of Peptidylglycine Α-Hydroxylating Monooxygenase By Cinnamic Acid Analogs, Neil R. Mcintyre, Edward W. Lowe Jr, Matthew R. Battistini, James W. Leahy, David J. Merkler
Chemistry Faculty Publications
Peptidylglycine α-amidating monooxygenase (PAM) is a bifunctional enzyme that catalyzes the final reaction in the maturation of α-amidated peptide hormones. Peptidylglycine α-hydroxylating monooxygenase (PHM) is the PAM domain responsible for the copper-, ascorbate- and O2-dependent hydroxylation of a glycine-extended peptide. Peptidylamidoglycolate lyase is the PAM domain responsible for the Zn(II)-dependent dealkylation of the α-hydroxyglycine-containing precursor to the final α-amidated peptide. We report herein that cinnamic acid and cinnamic acid analogs are inhibitors or inactivators of PHM. The inactivation chemistry exhibited by the cinnamates exhibits all the attributes of a suicide-substrate. However, we find no evidence for the formation …
The Nicotine Metabolite, Cotinine, Alters The Assembly And Trafficking Of A Subset Of Nicotinic Acetylcholine Receptors, Ashley M. Fox, Faruk H. Moonschi, Christopher I. Richards
The Nicotine Metabolite, Cotinine, Alters The Assembly And Trafficking Of A Subset Of Nicotinic Acetylcholine Receptors, Ashley M. Fox, Faruk H. Moonschi, Christopher I. Richards
Chemistry Faculty Publications
Exposure to nicotine alters the trafficking and assembly of nicotinic receptors (nAChRs), leading to their up-regulation on the plasma membrane. Although the mechanism is not fully understood, nicotine-induced up-regulation is believed to contribute to nicotine addiction. The effect of cotinine, the primary metabolite of nicotine, on nAChR trafficking and assembly has not been extensively investigated. We utilize a pH-sensitive variant of GFP, super ecliptic pHluorin, to differentiate between intracellular nAChRs and those expressed on the plasma membrane to quantify changes resulting from cotinine and nicotine exposure. Similar to nicotine, exposure to cotinine increases the number of α4β2 receptors on the …
Comparison Of Crystal Structures Of 4-(Benzo[B]Thiophen-2-Yl)-5-(3,4,5-Trimethoxyphenyl)-2H-1,2,3-Triazole And 4-(Benzo[B]Thiophen-2-Yl)-2-Methyl-5-(3,4,5-Trimethoxyphenyl)-2H-1,2,3-Triazole, Narsimha Reddy Penthala, Nikhil Reddy Madadi, Shobanbabu Bommagani, Sean Parkin, Peter A. Crooks
Comparison Of Crystal Structures Of 4-(Benzo[B]Thiophen-2-Yl)-5-(3,4,5-Trimethoxyphenyl)-2H-1,2,3-Triazole And 4-(Benzo[B]Thiophen-2-Yl)-2-Methyl-5-(3,4,5-Trimethoxyphenyl)-2H-1,2,3-Triazole, Narsimha Reddy Penthala, Nikhil Reddy Madadi, Shobanbabu Bommagani, Sean Parkin, Peter A. Crooks
Chemistry Faculty Publications
The title compound, C19H17N3O3S (I), was prepared by a [3 + 2]cycloaddition azide condensation reaction using sodium azide and l-proline as a Lewis base catalyst. N-Methylation of compound (I) using CH3I gave compound (II), C20H19N3O3S. The benzothiophene ring systems in (I) and (II) are almost planar, with r.m.s deviations from the mean plane = 0.0205 (14) in (I) and 0.016 (2) Å in (II). In (I) and (II), the triazole rings make dihedral angles of 32.68 (5) and 10.43 (8)°, respectively, …
Thimerosal Exposure And The Role Of Sulfation Chemistry And Thiol Availability In Autism, Janet K. Kern, Boyd E. Haley, David A. Geier, Lisa K. Sykes, Paul G. King, Mark R. Geier
Thimerosal Exposure And The Role Of Sulfation Chemistry And Thiol Availability In Autism, Janet K. Kern, Boyd E. Haley, David A. Geier, Lisa K. Sykes, Paul G. King, Mark R. Geier
Chemistry Faculty Publications
Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg …
Amyloid Β-Peptide (1–42)-Induced Oxidative Stress In Alzheimer Disease: Importance In Disease Pathogenesis And Progression, D. Allan Butterfield, Aaron M. Swomley, Rukhsana Sultana
Amyloid Β-Peptide (1–42)-Induced Oxidative Stress In Alzheimer Disease: Importance In Disease Pathogenesis And Progression, D. Allan Butterfield, Aaron M. Swomley, Rukhsana Sultana
Chemistry Faculty Publications
Significance: Alzheimer disease (AD) is an age-related neurodegenerative disease. AD is characterized by progressive cognitive impairment. One of the main histopathological hallmarks of AD brain is the presence of senile plaques (SPs) and another is elevated oxidative stress. The main component of SPs is amyloid beta-peptide (Aβ) that is derived from the proteolytic cleavage of amyloid precursor protein.
Recent Advances: Recent studies are consistent with the notion that methionine present at 35 position of Aβ is critical to Aβ-induced oxidative stress and neurotoxicity. Further, we also discuss the signatures of oxidatively modified brain proteins, identified using redox proteomics approaches, during …
Lipopolysaccharide Impairs Amyloid Β Efflux From Brain: Altered Vascular Sequestration, Cerebrospinal Fluid Reabsorption, Peripheral Clearance And Transporter Function At The Blood-Brain Barrier, Michelle A. Erickson, Pehr E. Hartvigson, Yoichi Morofuji, Joshua B. Owen, D. Allan Butterfield, William A. Banks
Lipopolysaccharide Impairs Amyloid Β Efflux From Brain: Altered Vascular Sequestration, Cerebrospinal Fluid Reabsorption, Peripheral Clearance And Transporter Function At The Blood-Brain Barrier, Michelle A. Erickson, Pehr E. Hartvigson, Yoichi Morofuji, Joshua B. Owen, D. Allan Butterfield, William A. Banks
Chemistry Faculty Publications
BACKGROUND: Defects in the low density lipoprotein receptor-related protein-1 (LRP-1) and p-glycoprotein (Pgp) clearance of amyloid beta (Aβ) from brain are thought to contribute to Alzheimer's disease (AD). We have recently shown that induction of systemic inflammation by lipopolysaccharide (LPS) results in impaired efflux of Aβ from the brain. The same treatment also impairs Pgp function. Here, our aim is to determine which physiological routes of Aβ clearance are affected following systemic inflammation, including those relying on LRP-1 and Pgp function at the blood-brain barrier.
METHODS: CD-1 mice aged between 6 and 8 weeks were treated with 3 intraperitoneal injections …
Oxidative Stress In Hpv-Driven Viral Carcinogenesis: Redox Proteomics Analysis Of Hpv-16 Dysplastic And Neoplastic Tissues, Federico De Marco, Elona Bucaj, Cesira Foppoli, Ada Fiorini, Carla Blarzino, Kozeta Filipi, Alessandra Giorgi, Maria Eugenia Schininà, Fabio Di Domenico, Raffaella Coccia, D. Allan Butterfield, Marzia Perluigi
Oxidative Stress In Hpv-Driven Viral Carcinogenesis: Redox Proteomics Analysis Of Hpv-16 Dysplastic And Neoplastic Tissues, Federico De Marco, Elona Bucaj, Cesira Foppoli, Ada Fiorini, Carla Blarzino, Kozeta Filipi, Alessandra Giorgi, Maria Eugenia Schininà, Fabio Di Domenico, Raffaella Coccia, D. Allan Butterfield, Marzia Perluigi
Chemistry Faculty Publications
Genital infection by high risk Human Papillomavirus (HR-HPV), although recognized as the main etio-pathogenetic factor of cervical cancer, is not per se sufficient to induce tumour development. Oxidative stress (OS) represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. To gain insight into the role of OS in cervical cancer, HPV-16 positive tissues were collected from patients with invasive squamous cervical carcinoma, from patients with High Grade dysplastic HPV lesions and from patients with no clinical evidence of HPV lesions. After virological characterization, modulation of proteins involved in the redox status regulation was investigated. ERp57 and …
Oxidative Dna Damage In Mild Cognitive Impairment And Late-Stage Alzheimer's Disease, Mark A. Lovell, William R. Markesbery
Oxidative Dna Damage In Mild Cognitive Impairment And Late-Stage Alzheimer's Disease, Mark A. Lovell, William R. Markesbery
Chemistry Faculty Publications
Increasing evidence supports a role for oxidative DNA damage in aging and several neurodegenerative diseases including Alzheimer's disease (AD). Attack of DNA by reactive oxygen species (ROS), particularly hydroxyl radicals, can lead to strand breaks, DNA–DNA and DNA–protein cross-linking, and formation of at least 20 modified bases adducts. In addition, α,β-unsaturated aldehydic by-products of lipid peroxidation including 4-hydroxynonenal and acrolein can interact with DNA bases leading to the formation of bulky exocyclic adducts. Modification of DNA bases by direct interaction with ROS or aldehydes can lead to mutations and altered protein synthesis. Several studies of DNA base adducts in late-stage …