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- ACADM; Inborn error of metabolism; MCAD; Medium-chain acyl-coenzyme A dehydrogenase deficiency; Newborn screening; Octanoylcarnitine (1)
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Articles 1 - 16 of 16
Full-Text Articles in Enzymes and Coenzymes
Design, Synthesis, And Evaluation Of Dasatinib-Amino Acid And Dasatinib-Fatty Acid Conjugates As Protein Tyrosine Kinase Inhibitors, Rakesh Tiwari, Alex Brown, Neda Sadeghiani, Amir Nasrolahi Shirazi, Jared Bolton, Amanda Tse, Gennady M. Verkhivker, Keykavous Parang, Gongqin Sun
Design, Synthesis, And Evaluation Of Dasatinib-Amino Acid And Dasatinib-Fatty Acid Conjugates As Protein Tyrosine Kinase Inhibitors, Rakesh Tiwari, Alex Brown, Neda Sadeghiani, Amir Nasrolahi Shirazi, Jared Bolton, Amanda Tse, Gennady M. Verkhivker, Keykavous Parang, Gongqin Sun
Pharmacy Faculty Articles and Research
Derivatives of dasatinib were synthesized via esterification with 25 carboxylic acids including amino acids and fatty acids by extending the inhibitor to interact with more diverse sites and to improve specificity. Dasatinib-L-arginine derivative (Das-R, 7) was the most potent of the inhibitors tested with IC50 values of 4.4 nM, <0.25 nM, and <0.45 nM against Csk, Src, and Abl kinases, respectively. The highest selectivity ratio obtained in our study, 91.4 Csk/Src belonged to compound 18 (Das-C10) with an IC50 of 3.2 μM for Csk compared to 35 nM for Src. Furthermore, many compounds displayed increased selectivity toward Src, as compared with Abl. Compounds 15 (Das-E) and 13 (Das-C) demonstrated the largest gains (10.2 and 10.3 Abl/Src IC50 ratios). Das-R (IC50 = 2.06 μM) was significantly more potent than Das (IC50 = 26.3 μM) against Panc-1 cells while they both showed an IC50 < 51.2 pM against BV-173 and K562 cells. Molecular modeling and binding free energy simulations revealed a good agreement with the experimental results and rationalized differences in selectivity of the studied compounds. Integration of experimental and computational approaches in the design and biochemical screening of dasatinib derivatives facilitated rational engineering and diversification of dasatinib scaffold, providing useful insights into mechanisms of kinase selectivity.
Lack Of Cross-Reactivity Allergy Following A Switch From Alirocumab To Evolocumab, Matthew D. Stryker, Michael Kane, Robert Busch
Lack Of Cross-Reactivity Allergy Following A Switch From Alirocumab To Evolocumab, Matthew D. Stryker, Michael Kane, Robert Busch
Excerpts in Pharmacy Research Journal
The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and gain-of-function mutations were first described in 2003. The gain-of-function mutations observed were associated with low-density lipoprotein-cholesterol (LDL-C) levels in the 400’s, in addition to premature cardiovascular disease. Subsequent loss-of-function experiments conducted in mice demonstrated marked reductions in plasma cholesterol levels in the absence of PCSK9. Physiologically, PCSK9 serves as a chaperone protein and functions to reduce low-density lipoprotein (LDL) receptor recycling; consequently, less LDL-C is removed from circulation and serum lipid concentrations become elevated. Inhibition of PCSK9 prevents LDL receptor degradation and preserves receptor recycling to the hepatocyte surface; this in …
221 Newborn-Screened Neonates With Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency: Findings From The Inborn Errors Of Metabolism Collaborative, K Bentler, S Zhai, S Elsbecker, G Arnold, B Burton, J Vockley, C Cameron, S Hiner, M Edick, S Berry, J Thomas, M Dodge, R Singh, S Lakshman, David Kronn, Inborn Errors Of Metabolism Collaborative
221 Newborn-Screened Neonates With Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency: Findings From The Inborn Errors Of Metabolism Collaborative, K Bentler, S Zhai, S Elsbecker, G Arnold, B Burton, J Vockley, C Cameron, S Hiner, M Edick, S Berry, J Thomas, M Dodge, R Singh, S Lakshman, David Kronn, Inborn Errors Of Metabolism Collaborative
NYMC Faculty Publications
Introduction: There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods: Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism-Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results: The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcamitine (C8) value on first newborn screen was 11.2 …
Quef And Quef-Like: Diverse Chemistries In A Common Fold, Adriana Bon Ramos
Quef And Quef-Like: Diverse Chemistries In A Common Fold, Adriana Bon Ramos
Dissertations and Theses
The tunneling fold (T-Fold) superfamily is a small superfamily of enzymes found in organisms encompassing all kingdoms of life. Seven members have been identified thus far. Despite sharing a common three-dimensional structure these enzymes perform very diverse chemistries.
QueF is a bacterial NADPH-dependent oxidoreductase that catalyzes the reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ0) to a primary amine (preQ1) in the queuosine biosynthetic pathway. Previous work on this enzyme has revealed the mechanism of reaction but the cofactor binding residues remain unknown. The experiments discussed herein aim to elucidate the role of residues lysine 80, …
Sweetening Of Glutamine Metabolism In Cancer Cells By Rho Gtpases Through Convergence Of Multiple Oncogenic Signaling Pathways, Thambi Dorai, John T. Pinto, Arthur J. L. Cooper
Sweetening Of Glutamine Metabolism In Cancer Cells By Rho Gtpases Through Convergence Of Multiple Oncogenic Signaling Pathways, Thambi Dorai, John T. Pinto, Arthur J. L. Cooper
NYMC Faculty Publications
An Automated Syringe Pump System For Improving The Reproducibility Of Dynamic Hyperpolarized Mri Phantoms, Harlee G. Harrison
An Automated Syringe Pump System For Improving The Reproducibility Of Dynamic Hyperpolarized Mri Phantoms, Harlee G. Harrison
Dissertations & Theses (Open Access)
AN AUTOMATED SYRINGE PUMP SYSTEM FOR IMPROVING THE REPRODUCIBILITY OF DYNAMIC HYPERPOLARIZED MRI PHANTOMS
Harlee Grace Harrison, B.S.
Advisory Professor: James Bankson, Ph.D.
Magnetic Resonance Imaging (MRI) is a powerful tool in the diagnosis of cancer due to its ability to provide good soft tissue contrast and image resolution without the use of ionizing radiation. The use of hyperpolarized pyruvate as a contrast agent for tumor metabolism during MR scans has the potential to provide information about tumor metabolism in vivo that is not available from traditional imaging measurements or any other method. Hyperpolarization is achieved through dynamic nuclear polarization. …
The Degradation Of Pharmaceutical Pollutants In Wastewater Catalyzed By Chloroperoxidase And The Construction Of Chloroperoxidase H105r Mutant, Qinghao He
FIU Electronic Theses and Dissertations
Trace amounts of pharmaceuticals have been detected in water, from nanograms per liter to micrograms per liter, and have a negatively effect in the aquatic environment and an increased potential risk of drug poisoning for human and animals. In order to address the problem, drug degradation catalyzed by chloroperoxidase (CPO) has been investigated. CPO is a heme-containing glycoprotein secreted by the fungus, Caldariomyces fumago, it catalyzes two major types of oxidations, two one-electron oxidations as catalyzed by most peroxidases and two-electron oxidations which are rare for conventional peroxidases.
Five common drugs from a variety of classes which were persistent in …
Interaction Between Two E3 Ligases, Nedd8ylated Cullin And Hhari, Kheewoong Baek
Interaction Between Two E3 Ligases, Nedd8ylated Cullin And Hhari, Kheewoong Baek
Theses and Dissertations (ETD)
RBR (RING1-in between RING-RING2) is a special type of E3 ubiquitin ligase containing three zinc-binding RING (Really Interesting New Gene) domains, while adopting mechanisms of HECT (Homologous to E6-AP Carboxyl Terminus) for substrate ubiquitination. Most well known RBRs include Parkin and HOIP, which are associated with Parkinson’s disease and innate immune deficiency. However, it is not well known how the RBR proteins gain activity, as they are known to be autoinhibited. Here I show that a specific F430A, E431A, E503A triple mutation of RBR protein HHARI (Human homologue of Ariadne) and its interaction with NEDD8ylated cullin RING ligase can both …
Purification Of Lactate Dehydrogenase, Irene J. Wilson
Purification Of Lactate Dehydrogenase, Irene J. Wilson
Scholarly and Creative Works Conference (2015 - 2021)
Lactate dehydrogenase (LDH), sometimes referred to as lactic acid dehydrogenase, is an enzyme that is found in the cytoplasm of almost all living cells. It converts lactate and NAD+ (nicotinamide adenine dinucleotide) to pyruvate and NADH (nicotinamide adenine dinucleotide hydrogen), and it can also catalyze the reverse reaction. Heart muscle is highly oxygenated at all times; therefore, LDH catalyzes the reaction in the direction to form NADH and pyruvate, which is used in the Citric Acid Cycle to make energy for the cell via aerobic cellular respiration. When little or no oxygen (O2) is available to the cell, such as …
Biochemical Characterization Of Diamide Inhibitors With N-Acetylglucosaminidases Lytg From Bacillus Subtilis, Drew Phelan
Biochemical Characterization Of Diamide Inhibitors With N-Acetylglucosaminidases Lytg From Bacillus Subtilis, Drew Phelan
Honors Projects in Science and Technology
In recent years the frequency of antibiotic resistance has been on the rise creating a need for antibiotic development with specific and lethal targets. It has been recently reported that glycosyl trizole are a novel class of antibacterial agents (1). Further investigation on the antibacterial ability of glycosyl triazole inhibitors has shown that targets include exo-acting N-acetylglucosaminidases (GlcNAcase) LytG (Bacillus subtilis) and FlgJ (Salmonella enterica) of the GH73 family (2). The Glycoside Hydrolase Family 73 (GH73) is characterized by bacterial and viral glycoside hydrolase. This enzyme cleaves the β-1,4-glycosidic linkage between N-acetylglucosaminyl (NAG) and N-acetylmuramyl (NAM) of the carbohydrate backbone …
Selective Binding Of Airapl Tandem Uims To Lys48-Linked Tri-Ubiquitin Chains, Simin Rahighi, Ilauna Braunstein, Nicola Ternette, Benedikt Kessler, Masato Kawasaki, Ryuichi Kato, Tsutomu Matsui, Ariel Stanhill, Soichi Wakatsuki
Selective Binding Of Airapl Tandem Uims To Lys48-Linked Tri-Ubiquitin Chains, Simin Rahighi, Ilauna Braunstein, Nicola Ternette, Benedikt Kessler, Masato Kawasaki, Ryuichi Kato, Tsutomu Matsui, Ariel Stanhill, Soichi Wakatsuki
Pharmacy Faculty Articles and Research
Lys48-linked ubiquitin chains act as the main targeting signals for protein degradation by the proteasome. Here we report selective binding of AIRAPL, a protein that associates with the proteasome upon exposure to arsenite, to Lys48-linked tri-ubiquitin chains. AIRAPL comprises two ubiquitin-interacting motifs in tandem (tUIMs) that are linked through a flexible inter-UIM region. In the complex crystal structure UIM1 binds the proximal ubiquitin, whereas UIM2 (the double-sided UIM) binds non-symmetrically to the middle and distal ubiquitin moieties on either side of the helix. Specificity of AIRAPL for Lys48-linked ubiquitin chains is determined by UIM2, and the flexible inter-UIM linker increases …
Long-Term Velaglucerase Alfa Treatment In Children With Gaucher Disease Type 1 Naïve To Enzyme Replacement Therapy Or Previously Treated With Imiglucerase., Laurie Smith, William Rhead, Joel Charrow, Suma P. Shankar, Ashish Bavdekar, Nicola Longo, Rebecca Mardach, Paul Harmatz, Thomas Hangartner, Hak-Myung Lee, Eric Crombez, Gregory M. Pastores
Long-Term Velaglucerase Alfa Treatment In Children With Gaucher Disease Type 1 Naïve To Enzyme Replacement Therapy Or Previously Treated With Imiglucerase., Laurie Smith, William Rhead, Joel Charrow, Suma P. Shankar, Ashish Bavdekar, Nicola Longo, Rebecca Mardach, Paul Harmatz, Thomas Hangartner, Hak-Myung Lee, Eric Crombez, Gregory M. Pastores
Manuscripts, Articles, Book Chapters and Other Papers
BACKGROUND: Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427).
METHODS: Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30-60U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty.
RESULTS: The study included 24 pediatric patients. …
Understanding And Targeting The C-Terminal Binding Protein (Ctbp) Substrate-Binding Domain For Cancer Therapeutic Development, Benjamin L. Morris
Understanding And Targeting The C-Terminal Binding Protein (Ctbp) Substrate-Binding Domain For Cancer Therapeutic Development, Benjamin L. Morris
Theses and Dissertations
Cancer involves the dysregulated proliferation and growth of cells throughout the body. C-terminal binding proteins (CtBP) 1 and 2 are transcriptional co-regulators upregulated in several cancers, including breast, colorectal, and ovarian tumors. CtBPs drive oncogenic properties, including migration, invasion, proliferation, and survival, in part through repression of tumor suppressor genes. CtBPs encode an intrinsic dehydrogenase activity, utilizing intracellular NADH concentrations and the substrate 4-methylthio-2-oxobutyric acid (MTOB), to regulate the recruitment of transcriptional regulatory complexes. High levels of MTOB inhibit CtBP dehydrogenase function and induce cytotoxicity among cancer cells in a CtBP-dependent manner. While encouraging, a good therapeutic would utilize >100-fold …
Postprandial Paraoxonase 1 Activity Following Consumption Of Recommended Amounts Of Mixed Meals In Healthy Males, Noriko Kameyama, Chizuko Maruyama, Kazuhiko Kotani, Russell Caccavello, Alejandro Gugliucci, Sadako Matsui, Taro Maruyama
Postprandial Paraoxonase 1 Activity Following Consumption Of Recommended Amounts Of Mixed Meals In Healthy Males, Noriko Kameyama, Chizuko Maruyama, Kazuhiko Kotani, Russell Caccavello, Alejandro Gugliucci, Sadako Matsui, Taro Maruyama
Faculty Publications & Research of the TUC College of Osteopathic Medicine
Aim: Postprandial lipid level increases induce oxidative stress, which is involved in atherogenesis. The antioxidant properties of paraoxonase 1 (PON1) have attracted attention. However, changes in postprandial PON1 levels differ across prior studies, and changes in PON1 lactonase activity, potentially relevant to PON1 physiology, after the consumption of ordinary meals are unknown. Herein we evaluated postprandial serum lipid levels and PON1 changes following mixed-meal consumption of the amounts recommended for ordinary meals.
Methods: Nine healthy male volunteers consumed three different meals in a randomized cross-over design. The test meals were as follows: S, white rice; SMF, S with …
Human Anatomy And Physiology Preparatory Course: Part 1 Of 4 (Interactive), Carlos Liachovitzky
Human Anatomy And Physiology Preparatory Course: Part 1 Of 4 (Interactive), Carlos Liachovitzky
Open Educational Resources
The overall purpose of these preparatory course set of learning objectives is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.
These 40+ learning objectives to prepare for Human Anatomy and Physiology can be downloaded and played in a desktop, or laptop (windows exe file).
The entire course has four parts:
Each learning objective is followed by a set of multiple choice question similar to those found later in a Human Anatomy and Physiology course.
The organization and …
Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii
Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii
Theses and Dissertations
Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …