Use of Crotamine and Composition Verwendung Von Crotamin Und Zusammensetzung Utilisation De La Crotamine Et Composition

Total Page:16

File Type:pdf, Size:1020Kb

Use of Crotamine and Composition Verwendung Von Crotamin Und Zusammensetzung Utilisation De La Crotamine Et Composition (19) TZZ_¥¥ _T (11) EP 1 866 332 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07K 14/46 (2006.01) G01N 33/68 (2006.01) 17.09.2014 Bulletin 2014/38 A61K 47/42 (2006.01) (21) Application number: 06721611.9 (86) International application number: PCT/BR2006/000052 (22) Date of filing: 17.03.2006 (87) International publication number: WO 2006/096953 (21.09.2006 Gazette 2006/38) (54) Use of Crotamine and Composition Verwendung von Crotamin und Zusammensetzung Utilisation de la crotamine et composition (84) Designated Contracting States: (74) Representative: Denjean, Eric et al AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Cabinet Laurent & Charras HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI "Le Contemporain" SK TR 50, Chemin de la Bruyère 69574 Dardilly Cedex (FR) (30) Priority: 18.03.2005 BR PI0501037 (56) References cited: (43) Date of publication of application: • KERKIS A ET AL: "Crotamine is a novel cell- 19.12.2007 Bulletin 2007/51 penetratingprotein from the venom of rattlesnake crotalus durissus terrificus" FASEB,, vol. 18, 1 (73) Proprietor: Fundacao de Amparo a Pesquisa do September 2004 (2004-09-01), pages 1407-1409, Estado de Sao XP002478903 Paulo - FAPESP • MORRIS M C ET AL: "TRANSLOCATING CEP-05468-901 Sao Paulo, SP (BR) PEPTIDES AND PROTEINS AND THEIR USE FOR GENE DELIVERY" CURRENT OPINION IN (72) Inventors: BIOTECHNOLOGY, LONDON, GB, vol. 11, no. 5, • YAMANE, Tetsuo 1 October 2000 (2000-10-01), pages 461-466, Butantã XP001022944 ISSN: 0958-1669 Brazil 05579-010 São Paulo, Sp (BR) • FUTAKI SHIROH ET AL: "Arginine- rich peptides: • KERKIS, Irina An abundant source of membrane-permeable 01421-001 São Paulo, SP (BR) peptides having potential as carriers for • KERKIS, Alexandre intracellular protein delivery" JOURNAL OF 01421-001 São Paulo, SP (BR) BIOLOGICAL CHEMISTRY, AL, vol. 276, no. 8, 17 • BAPTISTA, Gandhi, Rádis November 2000 (2000-11-17), pages 5836-5840, 04084-006 São Paulo, Sp (BR) XP002210171 ISSN: 0021-9258 • HAYASHI, Mirian, Akemi, Furuie • OGUIURA ET AL: "New view on crotamine, a 01403-020 São Paulo, SP (BR) small basic polypeptide myotoxin from South • KONNO, Katsuhiro American rattlesnake venom" TOXICON, 05503-900 São Paulo, SP (BR) ELMSFORD, NY, US, vol. 46, no. 4, 15 September • DA SILVA, Alvaro, Rossan, B., P. 2005 (2005-09-15), pages 363-370, XP005045652 01324-001 São Paulo, SP (BR) ISSN: 0041-0101 • PEREIRA, Lygia, da Veiga 05508-900 São Paulo, SP (BR) • DE OLIVEIRA, Eduardo, Brandt 14049-900 Ribeirao Preto, SP (BR) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 866 332 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 1 866 332 B1 • KERKIS A. ET AL.: ’Crotamine is a novel cell- • SANTOS M C DOS ET AL: ’Purification and penetratingprotein from the venom of rattlesnake properties of a crotamine analog from Crotalus Crotalus durissus terrificus’ FASEB J. vol. 18, no. durissus ruruima venom’ TOXICON vol. 31, no. 2, 12, September 2004, pages 1407 - 1409, 1993, & IVTH PAN AMERICAN SYMPOSIUM ON XP002478903 ANIMAL, PLANT AND MICROBIAL TOXINS (IST); • NICASTRO G. ET AL.: ’Solution structure of CAMPINAS, BRAZIL; JULY 27-31, 1992, page 166, crotamine, a Na+ channel affecting toxin from XP008160555 ISSN: 0041-0101 -& DATABASE Crotalus durissus terrificus venome’ EUR. J. Uniprot, [Online] 11 October 2004 (2004-10-11), BIOCHEM. vol. 270, no. 9, May 2003, pages 1969 DOS SANTOS M C ET AL: "Purification and - 1979, XP003022428 properties of a crotamine analog from Crotalus • LUNDBERG P. ET AL.: ’A brief introduction to durissus ruruima venom", XP007921611, cell-penetrating peptides’ J. MOL. RECOGNIT. retrieved from Uniprot Database accession no. vol. 16, no. 5, September 2003 - October 2003, P63327 pages 227 - 233, XP003022429 • FRANC BENJAMIN L ET AL: "Breaching •G.Rádis- Baptista ET AL: "Nucleotide sequence biological barriers: protein translocation of crotamine isoform precursors from a single domains as tools for molecular imaging and South American rattlesnake (Crotalus durissus therapy", MOLECULAR IMAGING, MIT PRESS, terrificus)", Toxicon, vol. 37, no. 7, 1 July 1999 US, vol. 2, no. 4, 1 October 2003 (2003-10-01) , (1999-07-01), pages973-984, XP055055102, ISSN: pages 313-323, XP009118803, ISSN: 1535-3508, 0041-0101, DOI: 10.1016/S0041-0101(98)00226-8 DOI: 10.1162/153535003322750655 -& DATABASE Uniprot, [Online] 27 September 2004 (2004-09-27), BATISTIC R F ET AL: "Nucleotide sequence of crotamine isoform precursors from a single South American rattlesnake (Crotalus durissus terrificus)", XP007921613, retrieved from Uniprot Database accession no. O57540 -& DATABASE Uniprot, [Online] 27 September 2004 (2004-09-27), BATISTIC R F ET AL: "Structure and chromosomal localization of the gene for crotamine, a toxin from the South American rattlesnake, Crotalus durissus terrificus", XP007921618, retrieved from Uniprot Database accession no. Q9PWF3 -& DATABASE Uniprot, [Online] 27 September 2004 2 EP 1 866 332 B1 Description FIELD OF THE INVENTION 5 [0001] The present invention refers, in one aspect, to the uses of crotamine and compositions containing it, based on its novel characteristics of internalization into mammalian cells cytoplasm and nucleus, and of interaction with genetic material. [0002] In one of its aspects, the invention refers to a series of applications of crotamine in submicromolar amounts, in which the concentration range of this polypeptide is no longer toxic, besides still presenting its characteristics of cell 10 penetration, molecule transport to the surface, cytoplasm or cell nucleus and a particularly selective cell penetration into actively proliferating cells. [0003] In another aspect, the invention refers to compositions comprising a pharmaceutically effective concentration of crotamine and said compositions for use in the treatment of cancers, based on its characteristics of interaction with genetic material, such as DNA and RNA, and its cell selectivity. 15 BACKGROUND OF THE INVENTION TOXICITY 20 [0004] To the eyes of an expert in the art, and bearing in mind the knowledge in the state of the art, toxic characteristics of crotamine could not be incentive, and they may even inhibit, the research of its use for any beneficial purpose for human beings and other living organisms. [0005] Crotamine is a toxin, more specifically a myotoxin, isolated from the venom of South American rattlesnake, Crotalus durissus terrificus (Gonçalves, J. M. (1956), Estudos sobre Venenos de Serpentes Brasileiras, II - Crotalus 25 durissus crotaminicus, Subspécie Biológica, An. Acad. Brasileira Ciências 28, 365-367). Crotamine is one of the most abundant components in the venom of rattlesnake, corresponding to approximately 10% of dry weight of the venom. Crotamine is a basic polypeptide with low molecular weight of about 4,800 Daltons and with isoelectric point above 9.5. It is constituted by 42 amino acid residues (YKQCHKKGGHCFPKEKICLPPSSDFGKMDCRWRWKCCKKGSG, residues 23 to 64 of SEQ ID NO: 5), presenting six cysteines forming three disulphide bridges, and it is rich in basic amino acids, 30 such as lysine and arginine. DOS SANTOS et al. ((1993), Purification and properties of a crotamine analog from Crotalus durissus ruruima venom, Toxicon 31(2), 166) and RADIS-BAPTISTA et al. ((1999), Nucleotide sequence of crotamine isoform precursors from a single South American rattlesnake (Crotalus durissus terrificus), Toxicon 37(7), 973-984) reported a crotamine analog where the leucine residue at position 19 is replaced by isoleucine (SEQ ID NO: 4). [0006] When injected intraperitoneally, crotamine causes a quick paralysis, in less than 15 minutes, of the hind legs 35 of mice, which is the typical physiological effect of this toxin. Furthermore, difficulty in breathing and rigidity are also observed, suggesting veratrine-simile action (Gonçalves, J. M. (1956), as mentioned above. At cellular and molecular levels, crotamine induces an increase in the voltage-dependent sodium current (as mediated by sodium channels) by causing high depolarization (reduction of rest potential) of the membrane of myocites of muscle fibers next to motor plates - a mechanism which is prevented by tetradotoxin (TTX) (Hong, S. J., Chang, C. (1985), Electrophysiological 40 Studies of Myotoxin as Isolated from Prairie Rattlesnake (Crotalus viridis viridis) Venom on Murine Skeletal Muscle, Toxicon 23, 927-937). Consequently, the massive inflow of sodium ions causes dilatation of the sarcoplasmatic reticulum of myocites and the slow induction of myonecrosis restricted to the cells of skeletal muscles (Ownby, C. L., Cameron, M. S., Tu, A. T. (1976), Isolation of Myotoxin Component from Rattlesnake (Crotalus viridis viridis) Venom, Am. J. Pathol. 85,149-166). 45 [0007] KERKIS et al. ((2004), Crotamine is a novel cell-penetrating protein from the venom of rattlesnake Crotalus durissus terrificus, FASEB Journal 18, 1407-1409) reported the cellular uptake of Cy3-crotamine, as well as the fact that crotamine is a marker of actively proliferating living cells. [0008] This mechanism, through which crotamine exerts its toxicity, is similar to myotoxin-a from Crotalus viridis viridis, a more extensively studied toxin. 50 [0009] Crotamine is able to form dimers through linkages between disulphide chains, acquiring a form close to a sphere, which covalently links extra subunits. [0010] Therefore, there are no publications in the state of the art suggesting or indicating, in any form, benefits incurred from the effects of crotamine on living organisms. 55 CELL PENETRATION [0011] Cell-penetrating peptides (CPP, or "cell-translocating peptides") are known in the state of the art. A few char- acteristics of this type of peptide were already published, such as its cationic character, low molecular weight and high 3 EP 1 866 332 B1 content of basic amino acids.
Recommended publications
  • Mechanistic Insights Into Functional Characteristics of Native Crotamine
    Toxicon 146 (2018) 1e12 Contents lists available at ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon Mechanistic insights into functional characteristics of native crotamine Daniel Batista da Cunha a, Ana Vitoria Pupo Silvestrini a, Ana Carolina Gomes da Silva a, Deborah Maria de Paula Estevam b,Flavia Lino Pollettini b, Juliana de Oliveira Navarro a, Armindo Antonio^ Alves a, Ana Laura Remedio Zeni Beretta a, * Joyce M. Annichino Bizzacchi c, Lilian Cristina Pereira d, Maurício Ventura Mazzi a, a Graduate Program in Biomedical Sciences Hermínio Ometto University Center, UNIARARAS, 7 Av. Dr. Maximiliano Baruto, 500, CEP 13607-339, Araras, SP, Brazil b Graduate Program in Agrarian and Veterinary Sciences, State University Paulista Júlio de Mesquita Filho-UNESP, Jaboticabal, SP, Brazil c Blood Hemostasis Laboratory, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil d Department of Bioprocesses and Biotechnology, Faculty of Agronomic Sciences, State University Paulista Júlio Mesquita Filho-UNESP, Botucatu, SP, Brazil article info abstract Article history: The chemical composition of snake venoms is a complex mixture of proteins and peptides that can be Received 4 October 2017 pharmacologically active. Crotamine, a cell-penetrating peptide, has been described to have antimicro- Received in revised form bial properties and it exerts its effects by interacting selectively with different structures, inducing 6 March 2018 changes in the ion flow pattern and cellular responses. However, its real therapeutic potential is not yet Accepted 20 March 2018 fully known. Bearing in mind that crotamine is a promising molecule in therapeutics, this study inves- Available online 21 March 2018 tigated the action of purified molecule in three aspects: I) antibacterial action on different species of clinical interest, II) the effect of two different concentrations of the molecule on platelet aggregation, and Keywords: fi Crotalus durissus terrificus III) its effects on isolated mitochondria.
    [Show full text]
  • 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.
    [Show full text]
  • Identification of Crotasin, a Crotamine-Related Gene of Crotalus
    Toxicon 43 (2004) 751–759 www.elsevier.com/locate/toxicon Identification of crotasin, a crotamine-related gene of Crotalus durissus terrificus G. Ra´dis-Baptistaa,*, T. Kubob, N. Oguiurac, A.R.B. Prieto da Silvaa, M.A.F. Hayashid, E.B. Oliveirae, T. Yamanea aMolecular Toxinology Laboratory, Butantan Institute, Av. Vital Brazil 1500, Sa˜o Paulo 05503-900, Brazil bMolecular Neurophysiology Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba Central 6, Tsukuba 305-8566, Japan cLaboratory of Herpetology, Butantan Institute, Av. Vital Brazil 1500, Sa˜o Paulo 05503-900, Brazil dLaboratory of Biochemistry and Biophysics, Av. Vital Brazil 1500, Sa˜o Paulo 05503-900, Brazil eDepartment of Biochemistry, Faculty of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Ribeira˜ Preto 14049-900, Brazil Received 25 November 2003; accepted 25 February 2004 Abstract Crotamine is a cationic peptide (4.9 kDa, pI 9.5) of South American rattlesnake, Crotalus durissus terrificus’ venom. Its presence varies according to the subspecies or the geographical locality of a given species. At the genomic level, we observed the presence of 1.8 kb gene, Crt-p1, in crotamine-positive specimens and its absence in crotamine-negative ones. In this work, we described a crotamine-related 2.5 kb gene, crotasin (Cts-p2), isolated from crotamine-negative specimens. Reverse transcription coupled to polymerase chain reaction indicates that Cts-p2 is abundantly expressed in several snake tissues, but scarcely expressed in the venom gland. The genome of crotamine-positive specimen contains both Crt-p1 and Cts-p2 genes.
    [Show full text]
  • Identification of Crotasin, a Crotamine-Related Gene of Crotalus
    Toxicon 43 (2004) 751–759 www.elsevier.com/locate/toxicon Identification of crotasin, a crotamine-related gene of Crotalus durissus terrificus G. Ra´dis-Baptistaa,*, T. Kubob, N. Oguiurac, A.R.B. Prieto da Silvaa, M.A.F. Hayashid, E.B. Oliveirae, T. Yamanea aMolecular Toxinology Laboratory, Butantan Institute, Av. Vital Brazil 1500, Sa˜o Paulo 05503-900, Brazil bMolecular Neurophysiology Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba Central 6, Tsukuba 305-8566, Japan cLaboratory of Herpetology, Butantan Institute, Av. Vital Brazil 1500, Sa˜o Paulo 05503-900, Brazil dLaboratory of Biochemistry and Biophysics, Av. Vital Brazil 1500, Sa˜o Paulo 05503-900, Brazil eDepartment of Biochemistry, Faculty of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Ribeira˜ Preto 14049-900, Brazil Received 25 November 2003; accepted 25 February 2004 Abstract Crotamine is a cationic peptide (4.9 kDa, pI 9.5) of South American rattlesnake, Crotalus durissus terrificus’ venom. Its presence varies according to the subspecies or the geographical locality of a given species. At the genomic level, we observed the presence of 1.8 kb gene, Crt-p1, in crotamine-positive specimens and its absence in crotamine-negative ones. In this work, we described a crotamine-related 2.5 kb gene, crotasin (Cts-p2), isolated from crotamine-negative specimens. Reverse transcription coupled to polymerase chain reaction indicates that Cts-p2 is abundantly expressed in several snake tissues, but scarcely expressed in the venom gland. The genome of crotamine-positive specimen contains both Crt-p1 and Cts-p2 genes.
    [Show full text]
  • Toxin Transcripts in Crotalus Atrox Venom and in Silico Structures of Toxins
    University of Texas Rio Grande Valley ScholarWorks @ UTRGV Biology Faculty Publications and Presentations College of Sciences 6-17-2020 Toxin transcripts in Crotalus atrox venom and in silico structures of toxins Ying Jia The University of Texas Rio Grande Valley Ivan Lopez The University of Texas Rio Grande Valley Paulina Kowalski The University of Texas Rio Grande Valley Follow this and additional works at: https://scholarworks.utrgv.edu/bio_fac Part of the Animal Sciences Commons, Biology Commons, and the Pharmacology, Toxicology and Environmental Health Commons Recommended Citation Jia Y, Lopez I, Kowalski P. Toxin transcripts in Crotalus atrox venom and in silico structures of toxins. J Venom Res. 2020 Jun 17;10:18-22. This Article is brought to you for free and open access by the College of Sciences at ScholarWorks @ UTRGV. It has been accepted for inclusion in Biology Faculty Publications and Presentations by an authorized administrator of ScholarWorks @ UTRGV. For more information, please contact [email protected], [email protected]. ISSN: 2044-0324 J Venom Res, 2020, Vol 10, 18-22 RESEARCH REPORT Toxin transcripts in Crotalus atrox venom and in silico structures of toxins Ying Jia*, Ivan Lopez and Paulina Kowalski Biology Department, The University of Texas Rio Grande Valley, Brownsville, Texas 78520, USA *Correspondence to: Ying Jia, Email: [email protected] Received: 16 May 2020 | Revised: 15 June 2020 | Accepted: 16 June 2020 | Published: 17 June 2020 © Copyright The Author(s). This is an open access article, published under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0).
    [Show full text]
  • In Memoriam: Prof. Dr. Jose Roberto Giglio and His Contributions To
    Toxicon 89 (2014) 91e93 Contents lists available at ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon In memoriam: Prof. Dr. Jose Roberto Giglio and his contributions to toxinology abstract Keywords: In memoriam Prof. Dr. Jose R. Giglio (1934e2014) made a highly significant contribution to the field of Prof. Dr. Jose Roberto Giglio Toxinology. During 48 years devoted to research and teaching Prof Giglio published more Toxinology than 160 articles, with more than 4400 citations, in international journals, trained a vast amount of graduate and undergraduate students, and developed an international network of collaborators. Throughout these years, he worked with dedication and deep commit- ment to science, leaving an immortalized legacy. During his professional career he contributed mostly in the isolation, and biochemical and functional characterization of various protein toxins derived from animal venoms such as snakes, scorpions and spiders, in addition to his studies searching for alternative therapies for poisoning. Even after his departure, his presence and influence remains among his former students and in the outstanding legacy of his scientific contributions. 1. Introduction laboratory, Professor Giglio was instrumental to the consolidation of my professional career when he supported When, on the morning of April 10, 2014, I received by unquestioningly my first research project to be submitted telephone the news of the death of Prof. Dr. Jose R. Giglio to FAPESP in 1997. When choosing the project title, he said I (Fig. 1), a huge sense of loss and sadness came over my could submit it because he believed in my potential and mind, just as his family and his many friends and disciples had already had other opportunities to evaluate my work.
    [Show full text]
  • Selected Publications
    Publications 1. Stojanoski, V. et al. A Triple Mutant in the Ω-loop of TEM-1 β-lactamase Changes the Substrate Profile via a Large Conformational Change and an Altered General Base for Catalysis. Journal of Biological Chemistry 290, 10382-10394 (2015). 2. Stojanoski, V. et al. Structural Basis for Different Substrate Profiles of Two Closely Related Class D β-lactamases and their Inhibition by Halogens. Biochemistry (2015). 3. Serbzhinskiy, D. et al. Structure of an ADP-ribosylation factor, ARF1, from Entamoeba histolytica bound to Mg2+–GD P. Structural Biology and Crystallization Communications 71, 594-599 (2015). 4. Sarma, G.N. et al. D-AKAP2: PKA RII: PDZK1 ternary complex structure: Insights from the nucleation of a polyvalent scaffold. Protein Science 24, 105-116 (2015). 5. Ogden, K.M. et al. Structural basis for 2'-5'-oligoadenylate binding and enzyme activity of a viral RNase L antagonist. Journal of virology (2015). 6. Marapakala, K. et al. A disulfide-bond cascade mechanism for arsenic (III) S- adenosylmethionine methyltransferase. Biological Crystallography 71, 505-515 (2015). 7. Hilbert, B. et al. The Structure and Mechanism of the ATPase that Powers Viral Genome Packaging. The FASEB Journal 29, LB156 (2015). 8. Edwards, T.E. et al. Crystal structures of Mycobacterial MeaB and M M A A-like GTPases. Journal of structural and functional genomics 16, 91-99 (2015). 9. Sippel, K.H., Vyas, N.K., Zhang, W., Sankaran, B. & Quiocho, F.A. Crystal structure of the human fatty acid synthase enoyl-acyl carrier protein-reductase domain complexed with triclosan reveals allosteric protein-protein interface inhibition.
    [Show full text]
  • Ontogenetic Change in the Venom of Mexican Black- Tailed Rattlesnakes (Crotalus Molossus Nigrescens)
    toxins Article Ontogenetic Change in the Venom of Mexican Black- Tailed Rattlesnakes (Crotalus molossus nigrescens) Miguel Borja 1,2 , Edgar Neri-Castro 3,4 , Rebeca Pérez-Morales 2, Jason L. Strickland 5 , Roberto Ponce-López 3, Christopher L. Parkinson 5,6 , Jorge Espinosa-Fematt 7, Jorge Sáenz-Mata 1 , Esau Flores-Martínez 1, Alejandro Alagón 3 and Gamaliel Castañeda-Gaytán 1,* 1 Facultad de Ciencias Biológicas, Universidad Juárez del Estado de Durango, Av. Universidad s/n. Fracc. Filadelfia, C.P. 35010 Gómez Palacio, Dgo., Mexico; [email protected] (M.B.); [email protected] (J.S.-M.); [email protected] (E.F.-M.) 2 Facultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, Av. Artículo 123 s/n. Fracc. Filadelfia, Apartado Postal No. 51, C.P. 35010 Gómez Palacio, Dgo., Mexico; [email protected] 3 Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad 2001, Chamilpa, C.P. 62210 Cuernavaca, Mor., Mexico; [email protected] (E.N.-C.); [email protected] (R.P.-L.); [email protected] (A.A.) 4 Programa de Doctorado en Ciencias Biomédicas UNAM, C.P. 04510 México D.F., Mexico 5 Department of Biological Sciences, Clemson University, 190 Collings St., Clemson, SC 29634, USA; [email protected] (J.L.S.); [email protected] (C.L.P.) 6 Department of Forestry and Environmental Conservation, Clemson University, 190 Collings St., Clemson, SC 29634, USA 7 Facultad de Ciencias de la Salud, Universidad Juárez del Estado de Durango, Calz. Palmas 1, Revolución, 35050 Gómez Palacio, Dgo., Mexico; [email protected] * Correspondence: [email protected]; Tel.: +52-871-715-2077 Received: 31 October 2018; Accepted: 26 November 2018; Published: 1 December 2018 Abstract: Ontogenetic changes in venom composition have important ecological implications due the relevance of venom in prey acquisition and defense.
    [Show full text]
  • Unifying Structural Signature of Eukaryotic Α-Helical Host Defense Peptides
    Unifying structural signature of eukaryotic α-helical host defense peptides Nannette Y. Younta,b,c, David C. Weaverd, Ernest Y. Leee, Michelle W. Leee, Huiyuan Wanga,b,c, Liana C. Chana,b,c, Gerard C. L. Wonge,f,g, and Michael R. Yeamana,b,c,h,1 aDivision of Molecular Medicine, Department of Medicine, Los Angeles County Harbor–University of California, Los Angeles, Medical Center, Torrance, CA 90509; bDivision of Infectious Diseases, Department of Medicine, Los Angeles County Harbor–University of California, Los Angeles, Medical Center, Torrance, CA 90509; cLos Angeles Biomedical Research Institute, Department of Medicine, Harbor–University of California, Los Angeles, Medical Center, Torrance, CA 90502; dDepartment of Mathematics, University of California, Berkeley, CA 94720; eDepartment of Bioengineering, University of California, Los Angeles, CA 90095; fDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095; gCalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095; and hDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90024 Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved February 14, 2019 (received for review November 9, 2018) Diversity of α-helical host defense peptides (αHDPs) contributes to ficult to translate into first principles. Thus, whereas machine- immunity against a broad spectrum of pathogens via multiple func- learning–based classifiers can discriminate between HDPs and tions. Thus, resolving common structure–function relationships non-HDPs, none to date have yielded more generalizable defini- among αHDPs is inherently difficult, even for artificial-intelligence– tions of αHDPs in a formulaic manner. based methods that seek multifactorial trends rather than founda- Here, knowledge-based annotation and iterative pattern rec- tional principles.
    [Show full text]
  • New View on Crotamine, a Small Basic Polypeptide Myotoxin from South American Rattlesnake Venom
    Toxicon 46 (2005) 363–370 www.elsevier.com/locate/toxicon Mini-review New view on crotamine, a small basic polypeptide myotoxin from South American rattlesnake venom N. Oguiuraa,*, M. Boni-Mitakeb,G.Ra´dis-Baptistac aLaborato´rio de Herpetologia, Instituto Butantan, Av. Vital Brazil, 1500, Sa˜o Paulo 05503-900, SP-Brazil bServic¸o de Radioprotec¸a˜o, Instituto de Pesquisas Energe´ticas e Nucleares, IPEN/CNEN-SP, Av.Lineu Prestes 2242, Sa˜o Paulo 05508-000, SP-Brazil cDepartamento de Bioquı´mica e Biologia Molecular, Universidade Federal do Ceara´, Fortaleza 60455-760, CE-Brazil Received 17 February 2005; revised 10 May 2005; accepted 8 June 2005 Abstract Crotamine is a toxin from the Crotalus durissus terrificus venom, composed of 42 amino acid residues and three disulfide bridges. It belongs to a toxin family previously called Small Basic Polypeptide Myotoxins (SBPM) whose members are widely distributed through the Crotalus snake venoms. Comparison of SBPM amino acid sequences shows high similarities. Crotamine induces skeletal muscle spasms, leading to spastic paralysis of the hind limbs of mice, by interacting with sodium channels on muscle cells. The crotamine gene with 1.8 kbp is organized into three exons, which are separated by a long phase-1 and short phase-2 introns and mapped to chromosome 2. The three-dimensional structure of crotamine was recently solved and shares a structural topology with other three disulfide bond-containing peptide similar to human b-defensins and scorpion NaC channel toxin. Novel biological activities have been reported, such as the capacity to penetrate undifferentiated cells, to localize in the nucleus, and to serve as a marker of actively proliferating living cells.
    [Show full text]
  • Crotamine and Crotalicidin, Membrane Active Peptides from Crotalus
    Peptides 126 (2020) 170234 Contents lists available at ScienceDirect Peptides journal homepage: www.elsevier.com/locate/peptides Review Crotamine and crotalicidin, membrane active peptides from Crotalus durissus terrificus rattlesnake venom, and their structurally-minimized fragments for T applications in medicine and biotechnology Claudio Borges Falcaoa,b,1, Gandhi Radis-Baptistac,* a Laboratory of Biochemistry and Biotechnology, Graduate program in Pharmaceutical Sciences, Federal University of Ceara, Brazil b Peter Pan Association to Fight Childhood Cancer, Fortaleza, CE, 60410-770, Brazil c Laboratory of Biochemistry and Biotechnology, Graduate program in Pharmaceutical Sciences and Institute for Marine Sciences, Federal University of Ceara, Av da Abolição 3207, Fortaleza, CE, 60165-081, Brazil ARTICLE INFO ABSTRACT Keywords: A global public health crisis has emerged with the extensive dissemination of multidrug-resistant microorgan- Antimicrobial peptides isms. Antimicrobial peptides (AMPs) from plants and animals have represented promising tools to counteract Cell-Penetrating peptides those resistant pathogens due to their multiple pharmacological properties such as antimicrobial, anticancer, Crotamine immunomodulatory and cell-penetrating activities. In this review, we will focus on crotamine and crotalicidin, Crotalicidin which are two interesting examples of membrane active peptides derived from the South America rattlesnake NrTPs Crotalus durrisus terrificus venom. Their full-sequences and structurally-minimized fragments have potential Ctn[15–34] Encrypted peptides applications, as anti-infective and anti-proliferative agents and diagnostics in medicine and in pharmaceutical Anti-infective peptides biotechnology. Antiproliferative peptides 1. Introduction antibiotics available to treat their MDR infections [5,6]. 1.1. Antimicrobial drug resistance 1.2. Cancer chemotherapy resistance The surge and dissemination of drug resistant microorganisms have Drug resistance issues can also be found in malignant tumors.
    [Show full text]
  • Antivenomics As a Tool to Improve the Neutralizing Capacity of the Crotalic
    Teixeira-Araújo et al. Journal of Venomous Animals and Toxins including Tropical Diseases (2017) 23:28 DOI 10.1186/s40409-017-0118-7 SHORT REPORT Open Access Antivenomics as a tool to improve the neutralizing capacity of the crotalic antivenom: a study with crotamine Ricardo Teixeira-Araújo1,2, Patrícia Castanheira1, Leonora Brazil-Más2, Francisco Pontes1,2, Moema Leitão de Araújo3, Maria Lucia Machado Alves3, Russolina Benedeta Zingali1 and Carlos Correa-Netto1,2* Abstract Background: Snakebite treatment requires administration of an appropriate antivenom that should contain antibodies capable of neutralizing the venom. To achieve this goal, antivenom production must start from a suitable immunization protocol and proper venom mixtures. In Brazil, antivenom against South American rattlesnake (Crotalus durissus terrificus) bites is produced by public institutions based on the guidelines defined by the regulatory agency of the Brazilian Ministry of Health, ANVISA. However, each institution uses its own mixture of rattlesnake venom antigens. Previous works have shown that crotamine, a toxin found in Crolatus durissus venom, shows marked individual and populational variation. In addition, serum produced from crotamine-negative venoms fails to recognize this molecule. Methods: In this work, we used an antivenomics approach to assess the cross-reactivity of crotalic antivenom manufactured by IVB towards crotamine-negative venom and a mixture of crotamine-negative/crotamine-positive venoms. Results: We show that the venom mixture containing 20% crotamine and 57% crotoxin produced a strong immunogenic response in horses. Antivenom raised against this venom mixture reacted with most venom components including crotamine and crotoxin, in contrast to the antivenom raised against crotamine-negative venom.
    [Show full text]