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Substances That Target Tumor Metabolism
Biomedical Research 2011; 22 (2): 132-166 1181_On the metabolic origin of cancer: substances that target tumor metabolism. Maurice Israël 1 and Laurent Schwartz 2 1Biorebus 38 rue de Bassano 75008 Paris ; and 2 Av Aristide Briand 91440 Bures sur Yvette. France. 2LIX : Ecole Polytechnique Palaiseau France ; and Hôpital Pitié- Salpêtrière, service de radiothérapie, 75013 Paris. Abstract. Work from our group and others clearly suggest the key role of altered metabolism in cancer. The goal of this review is to summarize current knowledge on cancer metabolism, draw hy- pothesis explaining metabolic alterations and associated gene changes. Most importantly, we indicate a list of possible pharmacological targets. In short, tumor metabolism displays mixed glycolysis and neoglucogenesis features; most glycolitic enzymes are activate, but the pyruvate kinase and the pyruvate deshydrogenase are inhibited. This would result from an activation of their specific kinases, or from the inactivation of phosphatases, such as PP2A, regulated by me- thylation. In parallel, the phosphatase failure would enhance “tyrosine kinase receptor” signals, as occurs with oncogenes. Such signaling pathways are similar to those activated by insuline, or IGF- Growth hormone; they control mitosis, cell survival, carbohydrate metabolism. If for some reason, their regulation fails (oncogenes, PP2A methylation deficit, enhanced kinases…) a typical tumor metabolism starts the carcinogenic process. We also describe changes in the citric acid- urea cycles, polyamines, and show how body stores feed tumor metabolic pathways above and below “bottlenecks” resulting from wrongly switched enzymes. Studying the available lit- erature, we list a number of medications that target enzymes that are essential for tumor cells. -
Acid Hydrolysis of Saponins Extracted in Tincture
PLOS ONE RESEARCH ARTICLE Acid hydrolysis of saponins extracted in tincture 1 2 Jamie LoveID *, Casey R. SimonsID 1 Synapses, Millbrae Cottage, Mill of Fyall, Alyth, Scotland, United Kingdom, 2 Department of Chemistry and Biochemistry, Utah State University, Logan, Utah, United States of America * [email protected] Abstract a1111111111 a1111111111 a1111111111 Background a1111111111 a1111111111 Saponins are secondary metabolites from plants added to shampoos and beverages to make them foam, and the sapogenins released from them upon acid hydrolysis are com- monly used as starting materials for steroidal drugs. However, current methods embed the saponin in a thick ªgumº material consisting of multiple impurities. This gum limits access to OPEN ACCESS the saponin, reducing the efficiency of hydrolysis and requiring large amounts of heat, organic solvents and effort to recover the sapogenin. For centuries, herbalists have been Citation: Love J, Simons CR (2020) Acid hydrolysis of saponins extracted in tincture. PLoS making tinctures by soaking plant materials at room temperature, in mixtures of alcohol and ONE 15(12): e0244654. https://doi.org/10.1371/ water. Many herbal tinctures contain saponins floating freely in solution, gum free. The journal.pone.0244654 saponin from sarsaparilla (Smilax spp), sarsasaponin, yields the sapogenin, sarsasapo- Editor: Pasquale Avino, Universita degli Studi del genin, upon acid hydrolysis. The retail price of sarsasapogenin is very high but would be Molise, ITALY lower if the ªgum problemº could be avoided. Received: October 6, 2020 Accepted: December 11, 2020 Materials and methods Published: December 31, 2020 We incubated sarsaparilla tincture under different conditions of temperature, acidity and duration then used quantitative nuclear magnetic resonance (qNMR) to measure the amount Peer Review History: PLOS recognizes the benefits of transparency in the peer review of sarsasapogenin produced by hydrolysis as well as the amount of its epimer, smilagenin. -
Subtiligase-Catalyzed Peptide Ligation Amy M
Review Cite This: Chem. Rev. 2020, 120, 3127−3160 pubs.acs.org/CR Subtiligase-Catalyzed Peptide Ligation Amy M. Weeks*,† and James A. Wells*,†,‡ † Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California 94143, United States ‡ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94143, United States ABSTRACT: Subtiligase-catalyzed peptide ligation is a powerful approach for site- specific protein bioconjugation, synthesis and semisynthesis of proteins and peptides, and chemoproteomic analysis of cellular N termini. Here, we provide a comprehensive review of the subtiligase technology, including its development, applications, and impacts on protein science. We highlight key advantages and limitations of the tool and compare it to other peptide ligase enzymes. Finally, we provide a perspective on future applications and challenges and how they may be addressed. CONTENTS 6.1. Subtiligase-Catalyzed Thioester and Thioa- cid Synthesis for Peptide and Protein 1. Introduction 3128 Bioconjugation 3138 2. Using Proteases in Reverse for Peptide Bond 6.2. Peptide Segment Condensation 3139 Formation 3129 6.3. Peptide Cyclization 3140 2.1. Protease-Catalyzed Peptide Bond Synthesis 6.4. Total Protein Synthesis 3140 under Thermodynamic Control 3129 7. Application of Subtiligase for Site-Specific 2.2. Protease-Catalyzed Peptide Bond Synthesis Protein Bioconjugation 3141 under Kinetic Control 3129 7.1. Sequence and Structural Requirements for 3. Protein Engineering of Subtilisin for Improved N-Terminal Modification by Subtiligase 3142 Peptide Bond Synthesis 3129 7.1.1. Characterization of Sequence and 3.1. Mutation of the Catalytic Serine to Cysteine 3129 Structural Requirements 3142 3.2. -
Natural Products As Alternative Choices for P-Glycoprotein (P-Gp) Inhibition
Review Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition Saikat Dewanjee 1,*, Tarun K. Dua 1, Niloy Bhattacharjee 1, Anup Das 2, Moumita Gangopadhyay 3, Ritu Khanra 1, Swarnalata Joardar 1, Muhammad Riaz 4, Vincenzo De Feo 5,* and Muhammad Zia-Ul-Haq 6,* 1 Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India; [email protected] (T.K.D.); [email protected] (N.B.); [email protected] (R.K.); [email protected] (S.J.) 2 Department of Pharmaceutical Technology, ADAMAS University, Barasat, Kolkata 700126, India; [email protected] 3 Department of Bioechnology, ADAMAS University, Barasat, Kolkata 700126, India; [email protected] 4 Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal 18050, Pakistan; [email protected] 5 Department of Pharmacy, Salerno University, Fisciano 84084, Salerno, Italy 6 Environment Science Department, Lahore College for Women University, Jail Road, Lahore 54600, Pakistan * Correspondence: [email protected] (S.D.); [email protected] (V.D.F.); [email protected] (M.Z.-U.-H.) Academic Editor: Maria Emília de Sousa Received: 11 April 2017; Accepted: 15 May 2017; Published: 25 May 2017 Abstract: Multidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to P-glycoprotein (P-gp) and its down-regulation by natural bioactive molecules. P-gp, a unique ATP-dependent membrane transport protein, is one of those key regulators which are present in the lining of the colon, endothelial cells of the blood brain barrier (BBB), bile duct, adrenal gland, kidney tubules, small intestine, pancreatic ducts and in many other tissues like heart, lungs, spleen, skeletal muscles, etc. -
Cysteine Proteinases of Microorganisms and Viruses
ISSN 00062979, Biochemistry (Moscow), 2008, Vol. 73, No. 1, pp. 113. © Pleiades Publishing, Ltd., 2008. Original Russian Text © G. N. Rudenskaya, D. V. Pupov, 2008, published in Biokhimiya, 2008, Vol. 73, No. 1, pp. 317. REVIEW Cysteine Proteinases of Microorganisms and Viruses G. N. Rudenskaya1* and D. V. Pupov2 1Faculty of Chemistry and 2Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; fax: (495) 9393181; Email: [email protected] Received May 7, 2007 Revision received July 18, 2007 Abstract—This review considers properties of secreted cysteine proteinases of protozoa, bacteria, and viruses and presents information on the contemporary taxonomy of cysteine proteinases. Literature data on the structure and physicochemical and enzymatic properties of these enzymes are reviewed. High interest in cysteine proteinases is explained by the discovery of these enzymes mostly in pathogenic organisms. The role of the proteinases in pathogenesis of several severe diseases of human and animals is discussed. DOI: 10.1134/S000629790801001X Key words: cysteine proteinases, properties, protozoa, bacteria, viruses Classification and Catalytic Mechanism papain and related peptidases showed that the catalytic of Cysteine Proteinases residues are arranged in the following order in the polypeptide chain: Cys, His, and Asn. Also, a glutamine Cysteine proteinases are peptidyl hydrolases in residue preceding the catalytic cysteine is also important which the role of the nucleophilic group of the active site for catalysis. This residue is probably involved in the for is performed by the sulfhydryl group of a cysteine residue. mation of the oxyanion cavity of the enzyme. The cat Cysteine proteinases were first discovered and investigat alytic cysteine residue is usually followed by a residue of ed in tropic plants. -
Serine Proteases with Altered Sensitivity to Activity-Modulating
(19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants. -
Herbal Principles in Cosmetics Properties and Mechanisms of Action Traditional Herbal Medicines for Modern Times
Traditional Herbal Medicines for Modern Times Herbal Principles in Cosmetics Properties and Mechanisms of Action Traditional Herbal Medicines for Modern Times Each volume in this series provides academia, health sciences, and the herbal medicines industry with in-depth coverage of the herbal remedies for infectious diseases, certain medical conditions, or the plant medicines of a particular country. Series Editor: Dr. Roland Hardman Volume 1 Shengmai San, edited by Kam-Ming Ko Volume 2 Rasayana: Ayurvedic Herbs for Rejuvenation and Longevity, by H.S. Puri Volume 3 Sho-Saiko-To: (Xiao-Chai-Hu-Tang) Scientific Evaluation and Clinical Applications, by Yukio Ogihara and Masaki Aburada Volume 4 Traditional Medicinal Plants and Malaria, edited by Merlin Willcox, Gerard Bodeker, and Philippe Rasoanaivo Volume 5 Juzen-taiho-to (Shi-Quan-Da-Bu-Tang): Scientific Evaluation and Clinical Applications, edited by Haruki Yamada and Ikuo Saiki Volume 6 Traditional Medicines for Modern Times: Antidiabetic Plants, edited by Amala Soumyanath Volume 7 Bupleurum Species: Scientific Evaluation and Clinical Applications, edited by Sheng-Li Pan Traditional Herbal Medicines for Modern Times Herbal Principles in Cosmetics Properties and Mechanisms of Action Bruno Burlando, Luisella Verotta, Laura Cornara, and Elisa Bottini-Massa Cover art design by Carlo Del Vecchio. CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2010 by Taylor and Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-13: 978-1-4398-1214-3 (Ebook-PDF) This book contains information obtained from authentic and highly regarded sources. -
Multiple Myeloma Inhibitory Activity of Plant Natural Products
cancers Review Multiple Myeloma Inhibitory Activity of Plant Natural Products Karin Jöhrer 1 and Serhat Sezai Ҫiҫek 2,* 1 Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria; karin.joehrer@tkfi.at 2 Department of Pharmaceutical Biology, Kiel University, Gutenbergstraße 76, 24118 Kiel, Germany * Correspondence: [email protected] Simple Summary: Multiple myeloma is the second most common hematological cancer and is still incurable. Although enhanced understanding of the disease background and the development of novel therapeutics during the last decade resulted in a significant increase of overall survival time, almost all patients relapse and finally succumb to their disease. Therefore, novel medications are urgently needed. Nature-derived compounds still account for the majority of new therapeutics and especially for the treatment of cancer often serve as lead compounds in drug development. The present review summarizes the data on plant natural products with in vitro and in vivo activity against multiple myeloma until the end of 2020, focusing on their structure–activity relationship as well as the investigated pathways and involved molecules. Abstract: A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced Citation: Jöhrer, K.; Ҫiҫek, S.S. -
Medicinal Herbs Quick Reference Guide Revision 2*
Medicinal Herbs Quick Reference Guide * Revision 2 Julieta Criollo DNM, CHT Doctor of Natural Medicine Clinical Herbal Therapist Wellness Trading Post [email protected] www.wellnesstradingpost.com 604-760-6425 Copyright © 2004–2011 Julieta Criollo All rights reserved. Note to the reader This booklet is intended for educational purposes only. The information contained in it has been compiled from published books and material on plant medicine. Although the information has been reviewed for correctness, the publisher/author does not assume any legal responsibility and/or liability for any errors or omissions. Furthermore, herbal/plant medicine standards (plant identification, medicinal properties, preparations, dosage, safety precautions and contraindications, pharmacology, and therapeutic usage) are continuously evolving and changing as new research and clinical studies are being published and expanding our knowledge. Hence, readers are encouraged and advised to check the most current information available on plant medicine standards and safety. T his information is not intended to be a substitute for professional medical advice. Always seek the advice of a medical doctor or qualified health practitioner prior to starting any new treatment, or with any questions you may have regarding a medical condition. The publisher/author does not assume any legal responsibility and/or liability for the use of the information contained in this booklet. * Revision 1 updates: addition of color bars to the Herb Groups and the various Herb -
Proteolytic Enzymes in Grass Pollen and Their Relationship to Allergenic Proteins
Proteolytic Enzymes in Grass Pollen and their Relationship to Allergenic Proteins By Rohit G. Saldanha A thesis submitted in fulfilment of the requirements for the degree of Masters by Research Faculty of Medicine The University of New South Wales March 2005 TABLE OF CONTENTS TABLE OF CONTENTS 1 LIST OF FIGURES 6 LIST OF TABLES 8 LIST OF TABLES 8 ABBREVIATIONS 8 ACKNOWLEDGEMENTS 11 PUBLISHED WORK FROM THIS THESIS 12 ABSTRACT 13 1. ASTHMA AND SENSITISATION IN ALLERGIC DISEASES 14 1.1 Defining Asthma and its Clinical Presentation 14 1.2 Inflammatory Responses in Asthma 15 1.2.1 The Early Phase Response 15 1.2.2 The Late Phase Reaction 16 1.3 Effects of Airway Inflammation 16 1.3.1 Respiratory Epithelium 16 1.3.2 Airway Remodelling 17 1.4 Classification of Asthma 18 1.4.1 Extrinsic Asthma 19 1.4.2 Intrinsic Asthma 19 1.5 Prevalence of Asthma 20 1.6 Immunological Sensitisation 22 1.7 Antigen Presentation and development of T cell Responses. 22 1.8 Factors Influencing T cell Activation Responses 25 1.8.1 Co-Stimulatory Interactions 25 1.8.2 Cognate Cellular Interactions 26 1.8.3 Soluble Pro-inflammatory Factors 26 1.9 Intracellular Signalling Mechanisms Regulating T cell Differentiation 30 2 POLLEN ALLERGENS AND THEIR RELATIONSHIP TO PROTEOLYTIC ENZYMES 33 1 2.1 The Role of Pollen Allergens in Asthma 33 2.2 Environmental Factors influencing Pollen Exposure 33 2.3 Classification of Pollen Sources 35 2.3.1 Taxonomy of Pollen Sources 35 2.3.2 Cross-Reactivity between different Pollen Allergens 40 2.4 Classification of Pollen Allergens 41 2.4.1 -
Publicaciones Junio De 2018 a Junio De 2019
UNIVERSIDAD DE SONORA SECRETARÍA GENERAL ACADÉMICA DIRECCIÓN DE INVESTIGACIÓN Y POSGRADO Artículos Publicados en Revistas Arbitradas por Personal Académico de la Institución INFORME ANUAL DEL RECTOR JUNIO 2018 – JUNIO 2019 A N E X O S E G U N D O I N F O R M E 2 0 1 8 - 2 0 1 9 CUADRO 1E NÚMERO DE ARTÍCULOS ARBITRADOS PUBLICADOS POR UNIDAD, DIVISIÓN Y DEPARTAMENTO Revistas Unidad / División / Departamento Total Internacional Nacional Unidad Regional Centro División de Ciencias Biológicas y de la Salud Departamento de Agricultura y Ganadería 5 9 14 Departamento de Ciencias Químico-Biológicas 34 4 38 Departamento de Enfermería 3 3 6 Departamento de Investigaciones Científicas y Tecnológicas 36 12 48 Departamento de Investigación y Posgrado en Alimentos 26 8 34 Departamento de Medicina y Ciencias de la Salud 7 3 10 Departamento de Ciencias del Deporte y la Actividad Física 2 3 5 Departamento de Ciencias de la Salud (Cajeme) 1 2 3 Subtotal 114 44 158 División de Ciencias Económicas y Administrativas Departamento de Administración 0 4 4 Departamento de Contabilidad 3 1 4 Departamento de Economía 1 7 8 Subtotal 4 12 16 División de Ciencias Exactas y Naturales Departamento de Física 28 1 29 Departamento de Geología 9 6 15 Departamento de Matemáticas 17 2 19 Departamento de Investigación en Física 48 2 50 Subtotal 102 11 113 División de Ingeniería Departamento de Ingeniería Civil y Minas 1 5 6 Departamento de Ingeniería Industrial 9 3 12 Departamento de Ingeniería Química y Metalurgia 17 1 18 Departamento de Investigación en Polímeros y Materiales 32 2 34 Subtotal 59 11 70 Continúa .. -
Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Chronic Venous Insufficiency/CVI
Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Chronic Venous Insufficiency/CVI Chemical Activity Count (+)-AROMOLINE 1 (+)-CATECHIN 5 (+)-GALLOCATECHIN 1 (+)-HERNANDEZINE 1 (+)-PRAERUPTORUM-A 1 (+)-SYRINGARESINOL 1 (+)-SYRINGARESINOL-DI-O-BETA-D-GLUCOSIDE 1 (-)-ACETOXYCOLLININ 1 (-)-APOGLAZIOVINE 1 (-)-BISPARTHENOLIDINE 1 (-)-BORNYL-CAFFEATE 1 (-)-BORNYL-FERULATE 1 (-)-BORNYL-P-COUMARATE 1 (-)-CANADINE 1 (-)-EPICATECHIN 4 (-)-EPICATECHIN-3-O-GALLATE 1 (-)-EPIGALLOCATECHIN 1 (-)-EPIGALLOCATECHIN-3-O-GALLATE 2 (-)-EPIGALLOCATECHIN-GALLATE 3 (-)-HYDROXYJASMONIC-ACID 1 (-)-N-(1'-DEOXY-1'-D-FRUCTOPYRANOSYL)-S-ALLYL-L-CYSTEINE-SULFOXIDE 1 (1'S)-1'-ACETOXYCHAVICOL-ACETATE 1 (2R)-(12Z,15Z)-2-HYDROXY-4-OXOHENEICOSA-12,15-DIEN-1-YL-ACETATE 1 (7R,10R)-CAROTA-1,4-DIENALDEHYDE 1 (E)-4-(3',4'-DIMETHOXYPHENYL)-BUT-3-EN-OL 1 1,2,6-TRI-O-GALLOYL-BETA-D-GLUCOSE 1 1,7-BIS(3,4-DIHYDROXYPHENYL)HEPTA-4E,6E-DIEN-3-ONE 1 Chemical Activity Count 1,7-BIS(4-HYDROXY-3-METHOXYPHENYL)-1,6-HEPTADIEN-3,5-DIONE 1 1,8-CINEOLE 1 1-(METHYLSULFINYL)-PROPYL-METHYL-DISULFIDE 1 1-ETHYL-BETA-CARBOLINE 1 1-O-(2,3,4-TRIHYDROXY-3-METHYL)-BUTYL-6-O-FERULOYL-BETA-D-GLUCOPYRANOSIDE 1 10-ACETOXY-8-HYDROXY-9-ISOBUTYLOXY-6-METHOXYTHYMOL 1 10-GINGEROL 1 12-(4'-METHOXYPHENYL)-DAURICINE 1 12-METHOXYDIHYDROCOSTULONIDE 1 13',II8-BIAPIGENIN 1 13-HYDROXYLUPANINE 1 14-ACETOXYCEDROL 1 14-O-ACETYL-ACOVENIDOSE-C 1 16-HYDROXY-4,4,10,13-TETRAMETHYL-17-(4-METHYL-PENTYL)-HEXADECAHYDRO- 1 CYCLOPENTA[A]PHENANTHREN-3-ONE 2,3,7-TRIHYDROXY-5-(3,4-DIHYDROXY-E-STYRYL)-6,7,8,9-TETRAHYDRO-5H-