Peptide Therapeutics from Venom: Current Status and Potential ⇑ Michael W
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Tetrodotoxin
Niharika Mandal et al. / Journal of Pharmacy Research 2012,5(7),3567-3570 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info Tetrodotoxin: An intriguing molecule Niharika Mandal*, Samanta Sekhar Khora, Kanagaraj Mohanapriya, and Soumya Jal School of Biosciences and Technology, VIT University, Vellore-632013 Tamil Nadu, India Received on:07-04-2012; Revised on: 12-05-2012; Accepted on:16-06-2012 ABSTRACT Tetrodotoxin (TTX) is one of the most potent neurotoxin of biological origin. It was first isolated from puffer fish and it has been discovered in various arrays of organism since then. Its origin is still unclear though some reports indicate towards microbial origin. TTX selectively blocks the sodium channel, inhibiting action potential thereby, leading to respiratory paralysis. TTX toxicity is mainly caused due to consumption of puffer fish. No Known antidote for TTX exists. Treatment is symptomatic. The present review is therefore, an effort to give an idea about the distribution, origin, structure, pharmacol- ogy, toxicity, symptoms, treatment, resistance and application of TTX. Key words: Tetrodotoxin, Neurotoxin, Puffer fish. INTRODUCTION One of the most intriguing biotoxins isolated and described in the twentieth cantly more toxic than TTX. Palytoxin and maitotoxin have potencies nearly century is the neurotoxin, Tetrodotoxin (TTX, CAS Number [4368-28-9]). 100 times that of TTX and Saxitoxin, and all four toxins are unusual in being A neurotoxin is a toxin that acts specifically on neurons usually by interact- non-proteins. Interestingly, there is also some evidence for a bacterial bio- ing with membrane proteins and ion channels mostly resulting in paralysis. -
Examples of Successful Protein Expression with SUMO Reference Protein Type Family Kda System (Pubmed ID)
Examples of Successful Protein Expression with SUMO Reference Protein Type Family kDa System (PubMed ID) 23 (FGF23), human Growth factor FGF superfamily ~26 E. coli 22249723 SARS coronavirus (SARS-CoV) membrane 3C-like (3CL) protease Viral membrane protein protein 33.8 E. coli 16211506 5′nucleotidase-related apyrase (5′Nuc) Saliva protein (apyrase) 5′nucleotidase-related proteins 65 E. coli 20351782 Acetyl-CoA carboxylase 1 (ACC1) Cytosolic enzyme Family of five biotin-dependent carboxylases ~7 E. coli 22123817 Acetyl-CoA carboxylase 2 (ACC2) BCCP domain Cytosolic enzyme Family of five biotin-dependent carboxylases ~7 E. coli 22123817 Actinohivin (AH) Lectin Anti-HIV lectin of CBM family 13 12.5 E. coli DTIC Allium sativum leaf agglutinin (ASAL) Sugar-binding protein Mannose-binding lectins 25 E. coli 20100526 Extracellular matrix Anosmin protein Marix protein 100 Mammalian 22898776 Antibacterial peptide CM4 (ABP-CM4) Antibacterial peptide Cecropin family of antimicrobial peptides 3.8 E. coli 19582446 peptide from centipede venoms of Scolopendra Antimicrobial peptide scolopin 1 (AMP-scolopin 1) small cationic peptide subspinipes mutilans 2.6 E. coli 24145284 Antitumor-analgesic Antitumor-analgesic peptide (AGAP) peptide Multifunction scorpion peptide 7 E. coli 20945481 Anti-VEGF165 single-chain variable fragment (scFv) Antibody Small antibody-engineered antibody 30 E. coli 18795288 APRIL TNF receptor ligand tumor necrosis factor (TNF) ligand 16 E. coli 24412409 APRIL (A proliferation-inducing ligand, also named TALL- Type II transmembrane 2, TRDL-1 and TNFSF-13a) protein Tumor necrosis factor (TNF) family 27.51 E. coli 22387304 Aprotinin/Basic pancreatic trypsin inhibitor (BPTI) Inhibitor Kunitz-type inhibitor 6.5 E. -
Suppression of Potassium Conductance by Droperidol Has
Anesthesiology 2001; 94:280–9 © 2001 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Suppression of Potassium Conductance by Droperidol Has Influence on Excitability of Spinal Sensory Neurons Andrea Olschewski, Dr.med.,* Gunter Hempelmann, Prof., Dr.med., Dr.h.c.,† Werner Vogel, Prof., Dr.rer.nat.,‡ Boris V. Safronov, P.D., Ph.D.§ Background: During spinal and epidural anesthesia with opi- Naϩ conductance.5–8 The sensitivity of different compo- oids, droperidol is added to prevent nausea and vomiting. The nents of Naϩ current to droperidol has further been mechanisms of its action on spinal sensory neurons are not studied in spinal dorsal horn neurons9 by means of the well understood. It was previously shown that droperidol se- 10,11 lectively blocks a fast component of the Na؉ current. The au- “entire soma isolation” (ESI) method. The ESI Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/94/2/280/403011/0000542-200102000-00018.pdf by guest on 25 September 2021 thors studied the action of droperidol on voltage-gated K؉ chan- method allowed a visual identification of the sensory nels and its effect on membrane excitability in spinal dorsal neurons within the spinal cord slice and further pharma- horn neurons of the rat. cologic study of ionic channels in their isolated somata Methods: Using a combination of the patch-clamp technique and the “entire soma isolation” method, the action of droperi- under conditions in which diffusion of the drug mole- -dol on fast-inactivating A-type and delayed-rectifier K؉ chan- cules is not impeded by the connective tissue surround nels was investigated. -
Biological Toxins Fact Sheet
Work with FACT SHEET Biological Toxins The University of Utah Institutional Biosafety Committee (IBC) reviews registrations for work with, possession of, use of, and transfer of acute biological toxins (mammalian LD50 <100 µg/kg body weight) or toxins that fall under the Federal Select Agent Guidelines, as well as the organisms, both natural and recombinant, which produce these toxins Toxins Requiring IBC Registration Laboratory Practices Guidelines for working with biological toxins can be found The following toxins require registration with the IBC. The list in Appendix I of the Biosafety in Microbiological and is not comprehensive. Any toxin with an LD50 greater than 100 µg/kg body weight, or on the select agent list requires Biomedical Laboratories registration. Principal investigators should confirm whether or (http://www.cdc.gov/biosafety/publications/bmbl5/i not the toxins they propose to work with require IBC ndex.htm). These are summarized below. registration by contacting the OEHS Biosafety Officer at [email protected] or 801-581-6590. Routine operations with dilute toxin solutions are Abrin conducted using Biosafety Level 2 (BSL2) practices and Aflatoxin these must be detailed in the IBC protocol and will be Bacillus anthracis edema factor verified during the inspection by OEHS staff prior to IBC Bacillus anthracis lethal toxin Botulinum neurotoxins approval. BSL2 Inspection checklists can be found here Brevetoxin (http://oehs.utah.edu/research-safety/biosafety/ Cholera toxin biosafety-laboratory-audits). All personnel working with Clostridium difficile toxin biological toxins or accessing a toxin laboratory must be Clostridium perfringens toxins Conotoxins trained in the theory and practice of the toxins to be used, Dendrotoxin (DTX) with special emphasis on the nature of the hazards Diacetoxyscirpenol (DAS) associated with laboratory operations and should be Diphtheria toxin familiar with the signs and symptoms of toxin exposure. -
Animal Venom Derived Toxins Are Novel Analgesics for Treatment Of
Short Communication iMedPub Journals 2018 www.imedpub.com Journal of Molecular Sciences Vol.2 No.1:6 Animal Venom Derived Toxins are Novel Upadhyay RK* Analgesics for Treatment of Arthritis Department of Zoology, DDU Gorakhpur University, Gorakhpur, UP, India Abstract *Corresponding authors: Ravi Kant Upadhyay Present review article explains use of animal venom derived toxins as analgesics of the treatment of chronic pain and inflammation occurs in arthritis. It is a [email protected] progressive degenerative joint disease that put major impact on joint function and quality of life. Patients face prolonged inappropriate inflammatory responses and bone erosion. Longer persistent chronic pain is a complex and debilitating Department of Zoology, DDU Gorakhpur condition associated with a large personal, mental, physical and socioeconomic University, Gorakhpur, UttarPradesh, India. burden. However, for mitigation of inflammation and sever pain in joints synthetic analgesics are used to provide quick relief from pain but they impose many long Tel: 9838448495 term side effects. Venom toxins showed high affinity to voltage gated channels, and pain receptors. These are strong inhibitors of ion channels which enable them as potential therapeutic agents for the treatment of pain. Present article Citation: Upadhyay RK (2018) Animal Venom emphasizes development of a new class of analgesic agents in form of venom Derived Toxins are Novel Analgesics for derived toxins for the treatment of arthritis. Treatment of Arthritis. J Mol Sci. Vol.2 No.1:6 Keywords: Analgesics; Venom toxins; Ion channels; Channel inhibitors; Pain; Inflammation Received: February 04, 2018; Accepted: March 12, 2018; Published: March 19, 2018 Introduction such as the back, spine, and pelvis. -
Letter from the Desk of David Challinor December 1992 We Often
Letter from the Desk of David Challinor December 1992 We often identify poisonous animals as snakes even though no more than a quarter of these reptiles are considered venomous. Snakes have a particular problem that is ameliorated by venom. With nothing to hold its food while eating, a snake can only grab its prey with its open mouth and swallow it whole. Their jaws can unhinge which allows snakes to swallow prey larger in diameter than their own body. Clearly the inside of a snake's mouth and the tract to its stomach must be slippery enough for the prey animal to slide down whole, and saliva provides this lubricant. When food first enters our mouths and we begin to chew, saliva and the enzymes it contains immediately start to break down the material for ease of swallowing. We are seldom aware of our saliva unless our mouths become dry, which triggers us to drink. When confronted with a chocolate sundae or other favorite dessert, humans salivate. The very image of such "mouth watering" food and the anticipation of tasting it causes a reaction in our mouths which prepares us for a delightful experience. Humans are not the only animals that salivate to prepare for eating, and this fluid has achieved some remarkable adaptations in other creatures. scientists believe that snake venom evolved from saliva. Why it became toxic in certain snake species and not in others is unknown, but the ability to produce venom helps snakes capture their prey. A mere glancing bite from a poisonous snake is often adequate to immobilize its quarry. -
A Functional Nav1.7-Navab Chimera with a Reconstituted High-Affinity Protx-II Binding Site S
Supplemental material to this article can be found at: http://molpharm.aspetjournals.org/content/suppl/2017/06/23/mol.117.108712.DC1 1521-0111/92/3/310–317$25.00 https://doi.org/10.1124/mol.117.108712 MOLECULAR PHARMACOLOGY Mol Pharmacol 92:310–317, September 2017 Copyright ª 2017 by The American Society for Pharmacology and Experimental Therapeutics A Functional NaV1.7-NaVAb Chimera with a Reconstituted High-Affinity ProTx-II Binding Site s Ramkumar Rajamani, Sophie Wu, Iyoncy Rodrigo, Mian Gao, Simon Low, Lisa Megson, David Wensel, Rick L. Pieschl, Debra J. Post-Munson, John Watson, David R. Langley, Michael K. Ahlijanian, Linda J. Bristow, and James Herrington Molecular Discovery Technologies, Wallingford, Connecticut, Princeton, New Jersey, and Waltham, Massachusetts (R.R., S.W., I.R., M.G., S.L., L.M., D.W., D.R.L.); Discovery Biology (R.L.P., D.J.P.-M., M.K.A., L.J.B., J.H.) and Lead Discovery and Optimization (J.W.), Bristol-Myers Squibb Company, Wallingford, Connecticut Downloaded from Received March 6, 2017; accepted June 14, 2017 ABSTRACT The NaV1.7 voltage-gated sodium channel is implicated in part of the voltage sensor domain 2 (VSD2) of NaV1.7. Importantly, human pain perception by genetics. Rare gain of function this chimera, DII S1–S4, forms functional sodium channels and is molpharm.aspetjournals.org mutations in NaV1.7 lead to spontaneous pain in humans whereas potently inhibited by the NaV1.7 VSD2 targeted peptide toxin loss of function mutations results in congenital insensitivity to pain. ProTx-II. Further, we show by [125I]ProTx-II binding and surface Hence, agents that specifically modulate the function of NaV1.7 plasmon resonance that the purified DII S1–S4 protein retains high have the potential to yield novel therapeutics to treat pain. -
Role of the Inflammasome in Defense Against Venoms
Role of the inflammasome in defense against venoms Noah W. Palm and Ruslan Medzhitov1 Department of Immunobiology, and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520 Contributed by Ruslan Medzhitov, December 11, 2012 (sent for review November 14, 2012) Venoms consist of a complex mixture of toxic components that are Large, multiprotein complexes responsible for the activation used by a variety of animal species for defense and predation. of caspase-1, termed inflammasomes, are activated in response Envenomation of mammalian species leads to an acute inflamma- to various infectious and noninfectious stimuli (14). The activa- tory response and can lead to the development of IgE-dependent tion of inflammasomes culminates in the autocatalytic cleavage venom allergy. However, the mechanisms by which the innate and activation of the proenzyme caspase-1 and the subsequent – immune system detects envenomation and initiates inflammatory caspase-1 dependent cleavage and noncanonical (endoplasmic- – fl and allergic responses to venoms remain largely unknown. Here reticulum and Golgi-independent) secretion of the proin am- matory cytokines IL-1β and IL-18, which lack leader sequences. we show that bee venom is detected by the NOD-like receptor fl family, pyrin domain-containing 3 inflammasome and can trigger In addition, activation of caspase-1 leads to a proin ammatory cell death termed pyroptosis. The NLRP3 inflammasome con- activation of caspase-1 and the subsequent processing and uncon- “ ” ventional secretion of the leaderless proinflammatory cytokine sists of the sensor protein NLRP3, the adaptor apoptosis-as- sociated speck-like protein (ASC) and caspase-1. Damage to IL-1β in macrophages. -
Venom Week 2012 4Th International Scientific Symposium on All Things Venomous
17th World Congress of the International Society on Toxinology Animal, Plant and Microbial Toxins & Venom Week 2012 4th International Scientific Symposium on All Things Venomous Honolulu, Hawaii, USA, July 8 – 13, 2012 1 Table of Contents Section Page Introduction 01 Scientific Organizing Committee 02 Local Organizing Committee / Sponsors / Co-Chairs 02 Welcome Messages 04 Governor’s Proclamation 08 Meeting Program 10 Sunday 13 Monday 15 Tuesday 20 Wednesday 26 Thursday 30 Friday 36 Poster Session I 41 Poster Session II 47 Supplemental program material 54 Additional Abstracts (#298 – #344) 61 International Society on Thrombosis & Haemostasis 99 2 Introduction Welcome to the 17th World Congress of the International Society on Toxinology (IST), held jointly with Venom Week 2012, 4th International Scientific Symposium on All Things Venomous, in Honolulu, Hawaii, USA, July 8 – 13, 2012. This is a supplement to the special issue of Toxicon. It contains the abstracts that were submitted too late for inclusion there, as well as a complete program agenda of the meeting, as well as other materials. At the time of this printing, we had 344 scientific abstracts scheduled for presentation and over 300 attendees from all over the planet. The World Congress of IST is held every three years, most recently in Recife, Brazil in March 2009. The IST World Congress is the primary international meeting bringing together scientists and physicians from around the world to discuss the most recent advances in the structure and function of natural toxins occurring in venomous animals, plants, or microorganisms, in medical, public health, and policy approaches to prevent or treat envenomations, and in the development of new toxin-derived drugs. -
Ligand and Voltage Gated Ion Channels
Print ISSN: 2319-2003 | Online ISSN: 2279-0780 IJBCP International Journal of Basic & Clinical Pharmacology DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20170314 Review Article Drug targets: ligand and voltage gated ion channels Nilan T. Jacob* Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), ABSTRACT Puducherry, India The elucidation of a drug target is one of the earliest and most important steps in the drug discovery process. Ion channels encompassing both the ligand gated Received: 03 December 2016 and voltage gated types are the second most common drug targets after G- Revised: 07 December 2016 Protein Coupled Receptors (GPCR). Ion channels are basically pore forming Accepted: 27 December 2016 membrane proteins specialized for conductance of ions as per the concentration gradient. They are further broadly classified based on the energy (ATP) *Correspondence to: dependence into active ion channels/pumps and passive ion channels. Gating is Dr. Nilan T. Jacob, the regulatory mechanism of these ion channels by which binding of a specific Email: molecule or alteration in membrane potential induces conformational change in [email protected] the channel architecture to result in ion flow or its inhibition. Thus, the study of ligand and voltage gated ion channels becomes an important tool for drug Copyright: © the author(s), discovery especially during the initial stage of target identification. This review publisher and licensee Medip aims to describe the ligand and voltage gated ion channels along with discussion Academy. This is an open- on its subfamilies, channel architecture and key pharmacological modulators. access article distributed under the terms of the Creative Keywords: Drug targets, Ion channels, Ligand gated ion channels, Receptor Commons Attribution Non- Commercial License, which pharmacology, Voltage gated ion channels permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. -
Immune Drug Discovery from Venoms
Accepted Manuscript Immune drug discovery from venoms Rocio Jimenez, Maria P. Ikonomopoulou, J.A. Lopez, John J. Miles PII: S0041-0101(17)30352-5 DOI: 10.1016/j.toxicon.2017.11.006 Reference: TOXCON 5763 To appear in: Toxicon Received Date: 18 July 2017 Revised Date: 14 November 2017 Accepted Date: 18 November 2017 Please cite this article as: Jimenez, R., Ikonomopoulou, M.P., Lopez, J.A., Miles, J.J., Immune drug discovery from venoms, Toxicon (2017), doi: 10.1016/j.toxicon.2017.11.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Immune drug discovery from venoms Rocio Jimenez 1,2 , Maria P. Ikonomopoulou 2,3 , J.A. Lopez 1,2 and John J. Miles 1,2,3,4,5 1. Griffith University, School of Natural Sciences, Brisbane, Queensland, Australia 2. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia 3. School of Medicine, The University of Queensland, Brisbane, Australia 4. Centre for Biodiscovery and Molecular DevelopmentMANUSCRIPT of Therapeutics, AITHM, James Cook University, Cairns, Queensland, Australia 5. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom Corresponding author: A/Prof John J. Miles, Molecular Immunology Laboratory, Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, Queensland,ACCEPTED Australia E-mail: [email protected]. -
Microcystis Aeruginosa Toxin: Cell Culture Toxicity, Hemolysis, and Mutagenicity Assays W
APPLIED AND ENVIRONMENTAL MICROBIOLOGY. June 1982, p. 1425-1433 Vol. 43, No. 6 0099-2240/82/061425-09$02.00/0 Microcystis aeruginosa Toxin: Cell Culture Toxicity, Hemolysis, and Mutagenicity Assays W. 0. K. GRABOW,l* W. C. Du RANDT,1 O. W. PROZESKY,2 AND W. E. SCOTT1 National Institute for Water Research, Council for Scientific and Industrial Research, P.O. Box 395, Pretoria 0001,1 and National Institute for Virology, Johannesburg,2 South Africa Received 9 November 1981/Accepted 22 February 1982 Crude toxin was prepared by lyophilization and extraction of toxic Microcystis aeruginosa from four natural sources and a unicellular laboratory culture. The responses of cultures of liver (Mahlavu and PLC/PRF/5), lung (MRC-5), cervix (HeLa), ovary (CHO-Kl), and kidney (BGM, MA-104, and Vero) cell lines to these preparations did not differ significantly from one another, indicating that toxicity was not specific for liver cells. The results of a trypan blue staining test showed that the toxin disrupted cell membrane permeability within a few minutes. Human, mouse, rat, sheep, and Muscovy duck erythrocytes were also lysed within a few minutes. Hemolysis was temperature dependent, and the reaction seemed to follow first-order kinetics. Escherichia coli, Streptococcus faecalis, and Tetrahymena pyriformis were not significantly affected by the toxin. The toxin yielded negative results in Ames/Salmonella mutagenicity assays. Micro- titer cell culture, trypan blue, and hemolysis assays for Microcvstis toxin are described. The effect of the toxin on mammalian cell cultures was characterized by extensive disintegration of cells and was distinguishable from the effects of E.