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Evaluation of in Silico Approach for Prediction of Presence of Opioid Peptides in Wheat
Evaluation of in silico approach for prediction of presence of opioid peptides in wheat This is the Accepted version of the following publication Garg, Swati, Apostolopoulos, Vasso, Nurgali, Kulmira and Mishra, Vijay Kumar (2018) Evaluation of in silico approach for prediction of presence of opioid peptides in wheat. Journal of Functional Foods, 41. 34 - 40. ISSN 1756-4646 The publisher’s official version can be found at https://www.sciencedirect.com/science/article/pii/S1756464617307454 Note that access to this version may require subscription. Downloaded from VU Research Repository https://vuir.vu.edu.au/36577/ 1 1 Evaluation of in silico approach for prediction of presence of opioid peptides in wheat 2 gluten 3 Abstract 4 Opioid like morphine and codeine are used for the management of pain, but are associated 5 with serious side-effects limiting their use. Wheat gluten proteins were assessed for the 6 presence of opioid peptides on the basis of tyrosine and proline within their sequence. Eleven 7 peptides were identified and occurrence of predicted sequences or their structural motifs were 8 analysed using BIOPEP database and ranked using PeptideRanker. Based on higher peptide 9 ranking, three sequences YPG, YYPG and YIPP were selected for determination of opioid 10 activity by cAMP assay against µ and κ opioid receptors. Three peptides inhibited the 11 production of cAMP to varied degree with EC50 values of YPG, YYPG and YIPP were 5.3 12 mM, 1.5 mM and 2.9 mM for µ-opioid receptor, and 1.9 mM, 1.2 mM and 3.2 mM for κ- 13 opioid receptor, respectively. -
INVESTIGATION of NATURAL PRODUCT SCAFFOLDS for the DEVELOPMENT of OPIOID RECEPTOR LIGANDS by Katherine M
INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS By Katherine M. Prevatt-Smith Submitted to the graduate degree program in Medicinal Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. _________________________________ Chairperson: Dr. Thomas E. Prisinzano _________________________________ Dr. Brian S. J. Blagg _________________________________ Dr. Michael F. Rafferty _________________________________ Dr. Paul R. Hanson _________________________________ Dr. Susan M. Lunte Date Defended: July 18, 2012 The Dissertation Committee for Katherine M. Prevatt-Smith certifies that this is the approved version of the following dissertation: INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS _________________________________ Chairperson: Dr. Thomas E. Prisinzano Date approved: July 18, 2012 ii ABSTRACT Kappa opioid (KOP) receptors have been suggested as an alternative target to the mu opioid (MOP) receptor for the treatment of pain because KOP activation is associated with fewer negative side-effects (respiratory depression, constipation, tolerance, and dependence). The KOP receptor has also been implicated in several abuse-related effects in the central nervous system (CNS). KOP ligands have been investigated as pharmacotherapies for drug abuse; KOP agonists have been shown to modulate dopamine concentrations in the CNS as well as attenuate the self-administration of cocaine in a variety of species, and KOP antagonists have potential in the treatment of relapse. One drawback of current opioid ligand investigation is that many compounds are based on the morphine scaffold and thus have similar properties, both positive and negative, to the parent molecule. Thus there is increasing need to discover new chemical scaffolds with opioid receptor activity. -
Rubsicolins Are Naturally Occurring G-Protein-Biased Delta Opioid Receptor Peptides
bioRxiv preprint doi: https://doi.org/10.1101/433805; this version posted October 5, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Title page Title: Rubsicolins are naturally occurring G-protein-biased delta opioid receptor peptides Short title: Rubsicolins are G-protein-biased peptides Authors: Robert J. Cassell1†, Kendall L. Mores1†, Breanna L. Zerfas1, Amr H.Mahmoud1, Markus A. Lill1,2,3, Darci J. Trader1,2,3, Richard M. van Rijn1,2,3 Author affiliation: 1Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, 2Purdue Institute for Drug Discovery, 3Purdue Institute for Integrative Neuroscience, West Lafayette, IN 47907 †Robert J Cassell and Kendall Mores contributed equally to this work Corresponding author: ‡Richard M. van Rijn, Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907 (Phone: 765-494- 6461; Email: [email protected]) Key words: delta opioid receptor; beta-arrestin; natural products; biased signaling; rubisco; G protein-coupled receptor Abstract: 187 Figures: 2 Tables: 2 References: 27 1 bioRxiv preprint doi: https://doi.org/10.1101/433805; this version posted October 5, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The impact that β-arrestin proteins have on G-protein-coupled receptor trafficking, signaling and physiological behavior has gained much appreciation over the past decade. A number of studies have attributed the side effects associated with the use of naturally occurring and synthetic opioids, such as respiratory depression and constipation, to excessive recruitment of β-arrestin. -
Intravta Deltorphin, but Not DPDPE, Induces Place Preference in Ethanoldrinking Rats
ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 38, No. 1 January 2014 Intra-VTA Deltorphin, But Not DPDPE, Induces Place Preference in Ethanol-Drinking Rats: Distinct DOR-1 and DOR-2 Mechanisms Control Ethanol Consumption and Reward Jennifer M. Mitchell, Elyssa B. Margolis, Allison R. Coker, Daicia C. Allen, and Howard L. Fields Background: While there is a growing body of evidence that the delta opioid receptor (DOR) modu- lates ethanol (EtOH) consumption, development of DOR-based medications is limited in part because there are 2 pharmacologically distinct DOR subtypes (DOR-1 and DOR-2) that can have opposing actions on behavior. Methods: We studied the behavioral influence of the DOR-1-selective agonist [D-Pen2,D-Pen5]- Enkephalin (DPDPE) and the DOR-2-selective agonist deltorphin microinjected into the ventral tegmental area (VTA) on EtOH consumption and conditioned place preference (CPP) and the physio- logical effects of these 2 DOR agonists on GABAergic synaptic transmission in VTA-containing brain slices from Lewis rats. Results: Neither deltorphin nor DPDPE induced a significant place preference in EtOH-na€ıve Lewis rats. However, deltorphin (but not DPDPE) induced a significant CPP in EtOH-drinking rats. In con- trast to the previous finding that intra-VTA DOR-1 activity inhibits EtOH consumption and that this inhibition correlates with a DPDPE-induced inhibition of GABA release, here we found no effect of DOR-2 activity on EtOH consumption nor was there a correlation between level of drinking and deltorphin-induced change in GABAergic synaptic transmission. Conclusions: These data indicate that the therapeutic potential of DOR agonists for alcohol abuse is through a selective action at the DOR-1 form of the receptor. -
Opioid Receptorsreceptors
OPIOIDOPIOID RECEPTORSRECEPTORS defined or “classical” types of opioid receptor µ,dk and . Alistair Corbett, Sandy McKnight and Graeme Genes encoding for these receptors have been cloned.5, Henderson 6,7,8 More recently, cDNA encoding an “orphan” receptor Dr Alistair Corbett is Lecturer in the School of was identified which has a high degree of homology to Biological and Biomedical Sciences, Glasgow the “classical” opioid receptors; on structural grounds Caledonian University, Cowcaddens Road, this receptor is an opioid receptor and has been named Glasgow G4 0BA, UK. ORL (opioid receptor-like).9 As would be predicted from 1 Dr Sandy McKnight is Associate Director, Parke- their known abilities to couple through pertussis toxin- Davis Neuroscience Research Centre, sensitive G-proteins, all of the cloned opioid receptors Cambridge University Forvie Site, Robinson possess the same general structure of an extracellular Way, Cambridge CB2 2QB, UK. N-terminal region, seven transmembrane domains and Professor Graeme Henderson is Professor of intracellular C-terminal tail structure. There is Pharmacology and Head of Department, pharmacological evidence for subtypes of each Department of Pharmacology, School of Medical receptor and other types of novel, less well- Sciences, University of Bristol, University Walk, characterised opioid receptors,eliz , , , , have also been Bristol BS8 1TD, UK. postulated. Thes -receptor, however, is no longer regarded as an opioid receptor. Introduction Receptor Subtypes Preparations of the opium poppy papaver somniferum m-Receptor subtypes have been used for many hundreds of years to relieve The MOR-1 gene, encoding for one form of them - pain. In 1803, Sertürner isolated a crystalline sample of receptor, shows approximately 50-70% homology to the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the the genes encoding for thedk -(DOR-1), -(KOR-1) and orphan (ORL ) receptors. -
Opioid Peptides 49 Ryszard Przewlocki
Opioid Peptides 49 Ryszard Przewlocki Abbreviations ACTH Adrenocorticotropic hormone CCK Cholecystokinin CPA Conditioned place aversion CPP Conditioned place preference CRE cAMP response element CREB cAMP response element binding CRF Corticotrophin-releasing factor CSF Cerebrospinal fluid CTAP D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (m-opioid receptor antagonist) DA Dopamine DOP d-opioid peptide EOPs Endogenous opioid peptides ERK Extracellular signal-regulated kinase FSH Follicle-stimulating hormone GnRH Gonadotrophin-releasing hormone HPA axis Hypothalamo-pituitary-adrenal axis KO Knockout KOP k-opioid peptide LH Luteinizing hormone MAPK Mitogen-activated protein kinase MOP m-opioid peptide NOP Nociceptin opioid peptide NTS Nucleus tractus solitarii PAG Periaqueductal gray R. Przewlocki Department of Molecular Neuropharmacology, Institute of Pharmacology, PAS, Krakow, Poland Department of Neurobiology and Neuropsychology, Jagiellonian University, Krakow, Poland e-mail: [email protected] D.W. Pfaff (ed.), Neuroscience in the 21st Century, 1525 DOI 10.1007/978-1-4614-1997-6_54, # Springer Science+Business Media, LLC 2013 1526 R. Przewlocki PDYN Prodynorphin PENK Proenkephalin PNOC Pronociceptin POMC Proopiomelanocortin PTSD Posttraumatic stress disorder PVN Paraventricular nucleus SIA Stress-induced analgesia VTA Ventral tegmental area Brief History of Opioid Peptides and Their Receptors Man has used opium extract from poppy seeds for centuries for both pain relief and recreation. At the beginning of the nineteenth century, Serturmer first isolated the active ingredient of opium and named it morphine after Morpheus, the Greek god of dreams. Fifty years later, morphine was introduced for the treatment of postoper- ative and chronic pain. Like opium, however, morphine was found to be an addictive drug. -
Efficacy and Safety of Gluten-Free and Casein-Free Diets Proposed in Children Presenting with Pervasive Developmental Disorders (Autism and Related Syndromes)
FRENCH FOOD SAFETY AGENCY Efficacy and safety of gluten-free and casein-free diets proposed in children presenting with pervasive developmental disorders (autism and related syndromes) April 2009 1 Chairmanship of the working group Professor Jean-Louis Bresson Scientific coordination Ms. Raphaëlle Ancellin and Ms. Sabine Houdart, under the direction of Professor Irène Margaritis 2 TABLE OF CONTENTS Table of contents ................................................................................................................... 3 Table of illustrations .............................................................................................................. 5 Composition of the working group ......................................................................................... 6 List of abbreviations .............................................................................................................. 7 1 Introduction .................................................................................................................... 8 1.1 Context of request ................................................................................................... 8 1.2 Autism: definition, origin, practical implications ........................................................ 8 1.2.1 Definition of autism and related disorders ......................................................... 8 1.2.2 Origins of autism .............................................................................................. 8 1.1.2.1 Neurobiological -
The Role of Protein Convertases in Bigdynorphin and Dynorphin a Metabolic Pathway
Université de Montréal The Role of Protein Convertases in Bigdynorphin and Dynorphin A Metabolic Pathway par ALBERTO RUIZ ORDUNA Département de biomédecine vétérinaire Faculté de médecine vétérinaire Mémoire présenté à la Faculté de médecine vétérinaire en vue de l’obtention du grade de maître ès sciences (M.Sc.) en sciences vétérinaires option pharmacologie Décembre, 2015 © Alberto Ruiz Orduna, 2015 Résumé Les dynorphines sont des neuropeptides importants avec un rôle central dans la nociception et l’atténuation de la douleur. De nombreux mécanismes régulent les concentrations de dynorphine endogènes, y compris la protéolyse. Les Proprotéines convertases (PC) sont largement exprimées dans le système nerveux central et clivent spécifiquement le C-terminale de couple acides aminés basiques, ou un résidu basique unique. Le contrôle protéolytique des concentrations endogènes de Big Dynorphine (BDyn) et dynorphine A (Dyn A) a un effet important sur la perception de la douleur et le rôle de PC reste à être déterminée. L'objectif de cette étude était de décrypter le rôle de PC1 et PC2 dans le contrôle protéolytique de BDyn et Dyn A avec l'aide de fractions cellulaires de la moelle épinière de type sauvage (WT), PC1 -/+ et PC2 -/+ de souris et par la spectrométrie de masse. Nos résultats démontrent clairement que PC1 et PC2 sont impliquées dans la protéolyse de BDyn et Dyn A avec un rôle plus significatif pour PC1. Le traitement en C-terminal de BDyn génère des fragments peptidiques spécifiques incluant dynorphine 1-19, dynorphine 1-13, dynorphine 1-11 et dynorphine 1-7 et Dyn A génère les fragments dynorphine 1-13, dynorphine 1-11 et dynorphine 1-7. -
(D-Ala*)Deltorphin II: D,-Dependent Stereotypies and Stimulation of Dopamine Release in the Nucleus Accumbens
The Journal of Neuroscience, June 1991, 17(6): 1565-l 576 (D-Ala*)Deltorphin II: D,-dependent Stereotypies and Stimulation of Dopamine Release in the Nucleus Accumbens R. Longoni,’ L. Spina,’ A. Mulas,’ E. Carboni,’ L. Garau,’ P. Melchiorri,2 and G. Di Chiaral ‘Institute of Experimental Pharmacology and Toxicology, University of Cagliari, 09100 Cagliari, Italy and 21nstitute of Medical Pharmacology, University of Rome “La Sapienza,” 00185 Rome, Italy In order to investigate the relative role of central 6- and has been implicated in the stimulant actions of systemic opiates. F-opioid receptors in behavior, the effects of (D- Morphine-like opiates stimulate DA release preferentially in the Ala*)cleltorphin II, a natural Gopioid peptide, and PL017, nucleus accumbens (Di Chiara and Imperato, 1988a) and elicit a beta-casomorphin derivative specific for mu receptors, hypermotility sensitive to blockade by the DA D, receptor an- were compared after local intracerebral and intraventricular tagonist SCH 23390 (Longoni et al., 1987a). Intra-accumbens administration. lntracerebral infusion of the two peptides was infusion of opioid peptides elicits motor stimulation, but this done bilaterally in the limbic nucleus accumbens and in the action seems independent from DA, being resistant to classic ventral and dorsal caudate putamen of freely moving rats DA-receptor antagonists (neuroleptics; Pert and Sivit, 1977; Ka- through chronic intracerebral cannulas. After intra-accum- livas et al., 1983). Moreover, the syndrome elicited by intra- bens infusion, the two peptides elicited marked but opposite accumbens opiates is biphasic, as motor stimulation is typically behavioral effects: while (o-Ala2)deltorphin II evoked dose- preceded by motor inhibition and catalepsy (Costa11et al., 1978). -
NIDA Drug Supply Program Catalog, 25Th Edition
RESEARCH RESOURCES DRUG SUPPLY PROGRAM CATALOG 25TH EDITION MAY 2016 CHEMISTRY AND PHARMACEUTICS BRANCH DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES NATIONAL INSTITUTE ON DRUG ABUSE NATIONAL INSTITUTES OF HEALTH DEPARTMENT OF HEALTH AND HUMAN SERVICES 6001 EXECUTIVE BOULEVARD ROCKVILLE, MARYLAND 20852 160524 On the cover: CPK rendering of nalfurafine. TABLE OF CONTENTS A. Introduction ................................................................................................1 B. NIDA Drug Supply Program (DSP) Ordering Guidelines ..........................3 C. Drug Request Checklist .............................................................................8 D. Sample DEA Order Form 222 ....................................................................9 E. Supply & Analysis of Standard Solutions of Δ9-THC ..............................10 F. Alternate Sources for Peptides ...............................................................11 G. Instructions for Analytical Services .........................................................12 H. X-Ray Diffraction Analysis of Compounds .............................................13 I. Nicotine Research Cigarettes Drug Supply Program .............................16 J. Ordering Guidelines for Nicotine Research Cigarettes (NRCs)..............18 K. Ordering Guidelines for Marijuana and Marijuana Cigarettes ................21 L. Important Addresses, Telephone & Fax Numbers ..................................24 M. Available Drugs, Compounds, and Dosage Forms ..............................25 -
Review of the Potential Health Impact of Β-Casomorphins and Related Peptides 1
EFSA Scientific Report (2009) 231, 1-107 SCIENTIFIC COOPERATION AND ASSISTANCE SCIENTIFIC REPORT OF EFSA Review of the potential health impact of β-casomorphins 1 and related peptides Report of the DATEX Working Group on β-casomorphins (Question N° EFSA-Q-2008-379) Issued on 29 January 2009 WORKING GROUP MEMBERS Ivano De Noni, Richard J. FitzGerald, Hannu J. T. Korhonen, Yves Le Roux, Chris T. Livesey, Inga Thorsdottir, Daniel Tomé, Renger Witkamp. 1 For citation purposes: Scientific Report of EFSA prepared by a DATEX Working Group on the potential health impact of β-casomorphins and related peptides. EFSA Scientific Report (2009) 231, 1-107 © European Food Safety Authority, 2009 Review of the potential health impact of β-casomorphins and related peptides SUMMARY Proteins are a very diverse family of large organic compounds involved in many important biological processes. Following their enzymatic hydrolysis during food processing or digestion, proteins may release fragments from their primary amino acid sequence. These fragments are called peptides, and many of them are known to be physiologically active. The possible beneficial effects of bioactive peptides have attracted increasing interest in recent years. On the other hand, there are also reports suggesting that some food-derived peptides might adversely affect human health. Among these, β-casomorphin-7 (BCM7), a peptide sequence present in the milk protein β-casein, has been suggested to contribute to an increased risk for certain non-communicable diseases, such as autism, cardiovascular diseases and type I diabetes. Some literature reports have proposed possible mechanistic explanations for such associations Recognising the alleged negative effect of BCM7 on human health, EFSA deemed it necessary to perform a comprehensive review of the published scientific literature in order to assess the relationship of this peptide and related peptides with non-communicable diseases. -
Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity
pharmaceutics Review Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity Junzhi Yang 1, Bianca G. Reilly 2, Thomas P. Davis 1,2 and Patrick T. Ronaldson 1,2,* 1 Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1295 N. Martin St., P.O. Box 210207, Tucson, AZ 85721, USA; [email protected] (J.Y.); [email protected] (T.P.D.) 2 Department of Pharmacology, College of Medicine, University of Arizona, 1501 N. Campbell Ave, P.O. Box 245050, Tucson, AZ 85724-5050, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-520-626-2173 Received: 19 September 2018; Accepted: 16 October 2018; Published: 18 October 2018 Abstract: Opioids are highly effective analgesics that have a serious potential for adverse drug reactions and for development of addiction and tolerance. Since the use of opioids has escalated in recent years, it is increasingly important to understand biological mechanisms that can increase the probability of opioid-associated adverse events occurring in patient populations. This is emphasized by the current opioid epidemic in the United States where opioid analgesics are frequently abused and misused. It has been established that the effectiveness of opioids is maximized when these drugs readily access opioid receptors in the central nervous system (CNS). Indeed, opioid delivery to the brain is significantly influenced by the blood-brain barrier (BBB). In particular, ATP-binding cassette (ABC) transporters that are endogenously expressed at the BBB are critical determinants of CNS opioid penetration. In this review, we will discuss current knowledge on the transport of opioid analgesic drugs by ABC transporters at the BBB.