Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2017-05-17T11:44:30Z
No. of bitstreams: 1
2016 - Francis Barbosa Ferreira.pdf: 4527522 bytes, checksum: 6a5a6589610ff851e68801c3ec05e3c9 (MD5) / Made available in DSpace on 2017-05-17T11:44:30Z (GMT). No. of bitstreams: 1
2016 - Francis Barbosa Ferreira.pdf: 4527522 bytes, checksum: 6a5a6589610ff851e68801c3ec05e3c9 (MD5)
Previous issue date: 2016-08-04 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / In this work, semi and thiosemicarbazones selected from the LaDMol-QM library, were used
to study their interactions with a metalloproteinase from the snake Bothrops pauloensis
(BpMP-I) by molecular modelling and enzymatic inhibition assays with the toxin. The
crystalographic structure of BaPI (PDB code: 2W12) was used as a mold to build the 3D
model of BpMP-I by homology modeling. The theorical model of BpMP-I showed good
quality parameters and was used in a subsequent molecular modeling study. The
thiossemicarbazones showed better molecular docking results and in vitro enzymatic
inhibitions assays than semicarbazones. Studies by semi-empirical methods indicate a positive
enthalpy of interaction, suggesting that the enzyme inhibition by these compounds must be a
entropy-driven process. The results were used together to select the LDQM-IN-23 compound
and propose rationally designed modifications to improve the interactions with the toxin. The
study of the catalytic site of BpMP-I showed that there is an adjacent pocket with amino
groups of the peptide bonds available for interaction. All results were used together to design
structural changes, aiming the enhancing of the interaction with toxin. Therefore, was
proposed the insertion of the carboxyl group with different spacers, containing 2 (LDQM-IN-
23b) and 3 methylene groups (LDQM-IN-23c). The docking results and semi-empiric
optimization showed that there was a considerable improvement in the interaction for the
modified compounds. The modified compounds were synthesized and tested for biological
and enzymatic inhibition activity. It was observed that the IC50 values have improved: the
original molecule, LDQM-IN-23 has an IC50 of 3,011 ?M and the modified molecules have
IC50 of 79.12 (LDQM-IN-23b) and 1.77 ?M (LDQM-IN-23c). These molecules were tested
for inhibition of hemorrhagic activity induced by Bothropoidin, a P-III class
metalloproteinase, and by the B. pauloensis whole snake venom. The three molecules can
inhibit the hemorrhagic activity induced by isolated toxin and whole venom, and LDQM-IN-
23c showed higher efficiency compared with the other two, and in a rate of 1:10 (w/w
venom/inhibitor) the inhibition of the hemorrhagic activity was 100%. A molecular docking
study of this lead compound with Snake Venom Metalloproteases (SVMPs) from different
snake species and genera showed that this molecule can effectivelly interact with these
SVMPs. / Neste trabalho, foram utilizadas semi e tiossemicarbazonas, selecionadas na quimioteca do
LaDMol-QM (Dequim-UFRRJ), para o estudo das intera??es destas com o s?tio ativo de uma
metaloprotease da pe?onha da serpente Bothrops pauloensis por modelagem molecular e
ensaios de inibi??o da atividade enzim?tica e biol?gica sobre a toxina. A estrutura
cristalogr?fica de uma metaloprotease (BaPI) complexada com um inibidor (um
peptideomim?tico) (c?digo PDB 2W12) foi utilizada como molde para a constru??o do
modelo 3D da metaloprotease da pe?onha de B. pauloensis (BpMP-I). O modelo 3D te?rico
da BpMP-I, in?dito para esta toxina, apresentou bons par?metros de qualidade, sendo
considerado adequado para estudos de planejamento de ligantes baseado na estrutura. As
tiossemicarbazonas obtiveram melhores resultados, quando comparados com os resultados
das semicarbazonas, tanto para os ensaios de docagem molecular quanto para estudos de
inibi??o da atividade enzim?tica in vitro. Estudos por m?todos semiemp?ricos indicam uma
entalpia de intera??o positiva, sugerindo que a inibi??o enzim?tica por estes compostos deve
ser um processo controlado entropicamente. Os resultados foram utilizados para selecionar o
derivado LDQM-IN-23 e propor modifica??es estruturais planejadas racionalmente, visando
melhorar a intera??o deste com a toxina. O estudo do s?tio catal?tico da metaloprotease
mostrou que esta possui uma cavidade adjacente com grupos amino das liga??es pept?dicas
dispon?veis para intera??o. Foi proposta, ent?o, a inser??o de um grupo carboxilato com
diferentes espa?adores, 2 (LDQM-IN-23b) e 3 grupos metileno (LDQM-IN-23c). Os
resultados de docagem e otimiza??o semi-emp?rica mostraram que houve uma melhora
consider?vel na intera??o dos ligantes modificados, os quais foram sintetizados e testados
para as atividades de inibi??o enzim?tica e biol?gica. Na inibi??o enzim?tica, houve melhora
da CI50 com o aumento do espa?ador. O composto LDQM-IN-23 tem CI50 de 3011,00 ?M e
os compostos modificados possuem a CI50 de 79,12 (LDQM-IN-23b) e 1,77 ?M (LDQM-IN-
23c). Estes compostos foram testados para a inibi??o da atividade hemorr?gica in vivo
induzida pela Botropoidina, uma metaloprotease da classe P-III, e pela pe?onha bruta de B.
pauloensis. Os tr?s compostos conseguiram inibir a atividade hemorr?gica induzida pela
toxina isolada e pela pe?onha, sendo que o composto LDQM-IN-23c mostrou maior
efici?ncia, quando comparado com os outros dois, e para a propor??o de 1:10 (m/m
pe?onha/inibidor) a inibi??o da atividade foi de 100%. Foi realizado um estudo de docagem
deste composto l?der com outras metaloproteases de pe?onha de serpentes (SVMPs ? Snake
Venom Metalloproteinases), de esp?cies e g?neros diferentes, mostrando que este ligante
consegue interagir com outras SVMPs e ? um candidato para inibir a atividade hemorr?gica
de SVMPs presentes na pe?onha, n?o s? de B. pauloensis, mas de outras serpentes
| Identifer | oai:union.ndltd.org:IBICT/oai:localhost:jspui/1655 |
| Date | 04 August 2016 |
| Creators | Ferreira, Francis Barbosa |
| Contributors | Sant'Anna, Carlos Mauricio Rabello de, ?vila, Veridiana de Melo Rodrigues, Albuquerque, Magaly Gir?o, Rodrigues, Renata Santos, Castro, Rosane Nora, Pontes, Emerson Guedes |
| Publisher | Universidade Federal Rural do Rio de Janeiro, Programa de P?s-Gradua??o em Qu?mica, UFRRJ, Brasil, Instituto de Ci?ncias Exatas |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFRRJ, instname:Universidade Federal Rural do Rio de Janeiro, instacron:UFRRJ |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | ACD/ChemSketch, Freeware version, Advanced Chemistry Development, Inc., Toronto, ON, Canada, www.acdlabs.com, 2015. AKAO, P. K.; TONOLI, C. C.; NAVARRO, M. S.; CINTRA, A. C.; NETO, J. R.; ARNI, R. K.; MURAKAMI, M. T. Structural studies of BmooMPalpha-I, a non-hemorrhagic metalloproteinase from Bothrops moojeni venom. Toxicon, v. 55, p. 361-368, 2010. AKAO, P. K. Caracteriza??o biof?sica e estrutural da metaloproteinase n?o-hemorr?gica do veneno de Bothrops moojeni e da endo-?-glicanase de Bacillus subtilis. Disserta??o de Mestrado, Universidade Estadual Paulista, S?o Jos? do Rio Preto, 2011. ALBUQUERQUE, N. H.; COSTA, T. B. G.; CAVALCANTI, M. L. F. Estudo dos acidentes of?dicos provocados por serpentes do g?nero Bothrops notificados no estado da Para?ba. Rev. de Biol. e Ci?n. da Terra, v. 5, n. 1, 1? sem., 2004. ALTSCHUL, S.F., GISH, W., MILLER, W., MYERS, E.W. & LIPMAN, D.J.. Basic local alignment search tool. Journal of Molecular Biology, 1990, 215, pp 403-410. AMARAL, A. A general consideration of snake poisoning and observations on Neotropical pit-vipers. Contributions of Harvard Institute of Tropical Biology and Medicine, v. 2, p. 1-64, 1925. ANDRADE-FILHO, A. An?lise cl?nico-epideiol?dica de casos de ofidismo atendidos em um hospital p?blico estadual de Minas Gerais de 2003 a 2012. Disseta??o de Mestrado, Belo Horizonte, Minas Gerais, Brasil, 2015. ANTUNES, A.; SANTOS, A. S.; SILVA, M. F.; RAGI, R.; BAGNATO, V. S. M?todo de Hartree-Fock: dois exemplos analiticamente sol?veis. Revista Brasileira de Ensino de F?sica, v. 21, p. 221-232, 1999. 66 ANTUNES, T. C.; YAMASHITA, K. M.; BARBARO, K. C.; SAIKI, M. SANTORO, M. L. Comparative analysis of newborn and adult Bothrops jararaca snake venoms. Toxicon, v. 56, p. 1443-1458, 2010. APTE, S. S. A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. Journal Biological Chemistry, v. 284, p. 31493-31497, 2009. ARNOLD, K.; BORDOLI, L.; KOPP, J.; SCHWEDE. T. The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling. Bioinformatics, vol. 22, p. 195-201, 2006. ATKINS, P. W.; PAULA, J. F?sico-Qu?mica. 7?ed., vol. 2, Rio de Janeiro (RJ): LTC Editora, 2004, 620 p. BARREIRO, E. J.; FRAGA, C. A. M. Qu?mica Medicinal: as bases moleculares da a??o dos f?rmacos. 3? Ed., Porto Alegre (RS): ArtMed, 2015, 608 p. BECKER, A.B.; ROTH, R.A. Identification of glutamate 169 as the binding third zinc residue in proteinase III, a member of the family of insulin-degrading enzymes. Biochemistry Journal, v. 292, p. 137-142, 1993. BENKERT, P.; BIASINI, M.; SCHWEDE, T. Toward the estimation of the absolute quality of individual proteins structure models. Bioinformatics, v. 27, p. 343-350, 2011. BERALDO, H. Semicarbazonas e tiossemicarbazonas: o amplo perfil farmacol?gico e usos cl?nicos. Qu?mica Nova, v. 27, p. 461-471, 2004. BERNARD, P.; SCIOR, T.; DIDIER, B.; HIBERT, M.; BERTHON, J. Y. Ethnopharmacology and bioinformatic combination for leads discovery: application to phospholipase A2 inhibitors. Phytochemistry, v. 58, p. 865-874, 2001. BERNSTEIN, H. J. README: RasMol 2.7.5. 2009. available at: http://www.openrasmol.org/software/rasmol/. Acessado em 04/2016. BIASINI, M.; BIENERT, S.; WATERHOUSE, A.; ARNOLD, K.; STUDER, G.; SCHMIDT, T.; KIEFER, F.; CASSARINO, T. G.; BERTONI, M.; BORDOLI, L.; SCHWEDE, T. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Research, v. 42, p. 252-258, 2014. BJARNASON, J.B., FOX, J.W. Hemorragic metalloproteinases from snake venoms. Pharmacology & Therapeutics, v. 62, p.325-372, 1994. BLOBEL, C.P. Metalloprotease- disintegrins: links to cell adhesion and cleavage of TNF alpha and Notch. Cell, v. 90, 589-592, 1997. BODE,W.; GOMIS-RUTH, F.X.; ST?CKLER, W. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the ?metzincs?. Federation of European Biochemical Societies FEBS Letters, v. 331, p. 134-140, 1993. 67 BORDOLI, L.; KIEFER, F.; ARNOLD, K.; BENKERT, P.; BATTEY, J.; SCHWEDE, T. Proteins structure homology modeling using SWISS-MODEL workspace. Nat. Protoc., v. 4, p. 1-13, 2009. BRADFORD, M. M. Rapid and sensitive method for the quatitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., n. 72, p. 248-254, 1976. BRAHMA, R. K.; McCLEARY, R. J. R.; KINI, R. M.; DOLEY, R. Venom gland transcriptomics for identifying, cataloging, and characterizing vemom proteins in snakes. Toxicon, v. 93, p. 1-10, 2015. BRASIL, Minist?rio da Sa?de. Dispon?vel em: http://portalsaude.saude.gov.br/images/pdf/2016/janeiro/20/1-Casos-Ofidismo-2000- 2015.pdf>. Acessado em 02/2016b. BRASIL, Minist?rio da Sa?de. Guia de Vigil?ncia Epidemiol?gica. Dispon?vel em: <bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_peconhentos.pdf >. Acessado em 02/2016a. BRAUD, S.; BON, C.; WISNER, A. Snake venom proteins acting on hemostasis. Biochimie, v. 82, p. 851-859, 2000. CADLE, J. E. Phylogenetic relationships among vipers: immunological evidence. In: CAMPBELL, J. A.; BRODIE Jr., E. D. (Eds). Biology of the pitvipers, Texas: Selva, p. 41- 48, 1992. CAL, E.; OBAYA, A.J.; LLAMAZARES, M.; GARABAYA, C.; QUESADA, V.; L?PEZOT?N, C. Cloning, expression analysis and structural characterization of seven novel human ADAMSs a Family of metalloproteinases with disintegrin and thrombosondin-1 domain. Gene, v. 283, 49-62, 2002. CALVETE, J. J.; SANZ, L.; ?NGULO, Y.; LOMONTE, B.; GUTI?RREZ, J. M. Venoms, venomics, antivenomics. FEBS Letters, v. 583, p. 1736-1743, 2009. CAMPBELL, J. A., LAMAR, W. W. 2004. The venomous reptiles of Latin American. Ithaca- New York, Comstock, v.2, 870p. CANTA?EDA, I. C. H.; PEREA?ES, J. A.; JIOS, J. L. Substituted thiobenzoic acid S-benzyl as potential inhibitors of a snake venom phospholipase A2: Synthesis, spectroscopic and computational studies. Journal of Molecular Structure, v. 1028, p. 7-12, 2012. CAVASOTTO, C. N.; PHATAK, S. S. Homology modeling in drug discovery: current trends and applications. Drug Discovery Today, v. 14, p. 676-683, 2009. CERD?-COSTA, N.; GOMIS-R?TH, F.X. Architecture and function of metallopeptidase catalytic domains. Protein Science, v. 23, p.123 ? 144, 2014. 68 CHENG. Y.; PRUSOFF, W. H. Ralationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacolo., v. 22, p. 3099-3108, 1973. CHOU, T. L.; WU, C. H.; HUANG, K. F.; WANG, A. H. Crystal structure of a Trimeresurus mucrosquamatus venom metalloproteinase providing new insights into the inhibition by endogenous tripeptide inhibitors. Toxicon, v. 71c, p. 140-146, 2013. CLARK, D. E.; KRAMER, R. D.; van OPDENBOSCH, N. Validation of the general-purpose TRIPOS 5.2 force-field. Journal of Computational Chemistry, v. 10, p. 982-1012, 1989. CORONADO, M.A.; MORAES, F.R.; ULLAH, A.; MASSOD, R.; SANTANA, V.S.; MARIUTTI, R.; BROGNARO, H.; GEORGIEVA, D.; MURAKAMI, M.T.; BETZEL, C.; ARNI, R.K. Three-dimensional structures and mechanisms of snake venom serine proteinases, metalloproteinases, and phospholipase A2s. Toxinology, v. 17, p. 1-25, 2014. COSTA, F. L. S.; RODRIGUES, R. S.; IZIDORO, L. F. M.; MENALDO, D. L.; HAMAGUCHI, A.; HOMSI-BRANDEBURGO, M. I.; FULY, A. L.; SOARES, S. G.; SELISTRE-DE-ARAUJO, H. S.; BARRAVIERA, B.; SOARES, A. M.; RODRIGUES, V. M. Biochemical and functional properties of a thrombin-like enzyme isolated from Bothrops pauloensis snake venom. Toxicon, v. 54, p. 725-735, 2009. COSTA, J. O.; FONSECA, K. C.; MAMEDE, C. C. N.; BELETTI, M. E.; SANTOS-FILHO, N. A.; SOARES, A. M.; ARANTES, E. C.; HIRAYAMA, S. N. S.; SELISTRE-DEARA?JO, H. S.; FONSECA, F.; HENRIQUE-SILVA, F.; PENHA-SILVA, N.; OLIVEIRA, F. Bhalternin: Functional and structural characterization of a new thrombin-like enzyme from Bothrops alternatus snake venom. Toxicon, v. 55, p. 1365-1377, 2010. COSTA-FILHO, P. A.; POPPI, R, J. Algoritmo gen?tico em qu?mica. Qu?mica Nova, v. 22, p. 405-411, 1999 COTRIM, C. A.; OLIVEIRA, S. C. B.; DIZ-FILHO, E. B. S.; FONSECA, F. V.; BALISSERA-JR, L.; ANTUNES, E.; XIMENES, R. M.; MONTEIRO, H. S. A.; RABELLO, M. M.; HERNANDES, M. Z.; TOYAMA, D. O.; TOYAMA, M. H. Quercetin as an inhibitor of snake venom secretory phospholipase A2. Chemico-Biological Interactions, v. 189, p. 9- 16, 2011. CUPO, P.; AZEVEDO-MARQUES, M. M.; MENEZES, J. B.; HERING, S. E. Rea??es de hipersenbilidade imediata ap?s uso intravenoso de soros antivenenos: valor progn?stico dos testes de sensibilidade intrad?rmicos. Ver. Inst. Med. Trop. S?o Paulo, v. 33, p. 115-122, 1991. DENNIS, E. A. The growing phospholipase A2 superfamily of signal transduction enzymes. TiBS, v. 22, p. 1-2, 1997. DESSEN, A. Structure and mechanism of human cytosolic phospholipase A2. Biochimica et Biophysica Acta, v. 1488, p. 40-47, 2000. 69 DEWAR, M. J. S.; ZOEBISCH, E. G.; HEALY, E. F.; STEWART, J. J. P. AM1: a new general purpose quantum mechanical molecular model. Journal of the American Chemical Society, p. 107, p. 3902-3909, 1985. ELDRIDGE, M. D.; MURRAY, C. W.; AUTON, T. R.; PAOLINI, G. V.; MEE, R. P. Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. Journal of Computer-Aided Molecular Design, v. 11, p. 425-445, 1997. FENWICK, A. M.; GUTBERLET JR, R. L.; EVANS, J. A.; PARKINSON, C. L. Morphological and molecular evidence for phylogeny and classification of South American pitvipers, genera Bothrops, Bothriopsis, and Bothrocophias (Serpentes: Viperidae). Zoological Journal of the Linnean Society, v. 156, p. 617-640, 2009. FERNANDES, W.; ABE, A. S. An eletrophoretic approach to the relationships among the subspedies of the lancehead Bothrops neuwiedi (Serpentes, Viperidae). Zool. Anz., v. 226, p. 195-201, 1991. FERREIRA, F. B.; GOMES, M. S. R.; NAVES-DE-SOUZA, D. L.; GIMENES, S. N. C.; CASTANHEIRA, L. E.; BORGES, M. H.; RODRIGUES, R. S.; YONEYAMA, K. A. G.; BRANDEBURGO, M. I. H.; RODRIGUES, V. M. Molecular cloning and pharmacological properties of na acidic PLA2 flrom Bothrops pauloensis, snake venom. Toxins, v. 5, p. 2403- 2419, 2013. FOX, J.W.; SERRANO, S.M.T. Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity. Federation of European Biochemical Societies (FEBS) Letters, v. 275, p 3016-3030, 2008. FRANCISCHETTI, I. M. B.; CASTRO, H. C.; ZINGALI, R. B.; CARLINI, C. R. and GUIMARAES, J. A. Bothrops sp. snake venoms: comparison of some biochemical and physicochemical properties and interference in platelet functions. Comp. Biochem. Physiol, v. 119c, p. 21-29, 1998. FREITAS, M. A.; GENO, P. W.; SUMMER, L. W.; COOKE, M. E.; HUDIBURG, S. A.; OWNBY, C. L.; KAISER, I. I.; ODELL, G. V. Citrate is a major component of snake venoms. Toxicon, v. 30, p. 461-464, 1992. GIBAS, C.; JAMBECK, P. Developing Bioinformatics Computer Skills. O?Reilly Media Inc., Sebastopol, CA, Estados Unidos, 1 Ed., 2001, 427 p. GIMENES, S. N. C.; FERREIRA, F. B.; SILVEIRA, A. C. P.; RODRIGUES, R. S.; YONEYAMA, K. A. G.; SANTOS, J. I.; FONTES, M. R. M.; BRITES, V. L. C.; SANTOS, A. L. Q.; BORGES, M. H.; LOPES, D. S.; RODRIGUES, V. M. Isolation and biochemical characterization of a ?-type phospholipases A2 inhibitor from Crotalus durissus collilineatus snake serum. Toxicon, v. 81, p. 58-66, 2014. GOMES, M. S. R.; NAVES-DE-SOUZA, D. L.; GUIMAR?ES, D. O.; LOPES, D. S.; MAMEDE, C. C. N.; GIMENES, S. N. C.; ACH?, D. C.; RODRIGUES, R. S.; YONEYAMA, K. A. G.; BORGES, M. H.; OLIVEIRA, F.; RODRIGUES, V. M. Biochemical and functional characterization of Bothropoidin: the first haemorrhagic 70 metalloproteinase from Bothrops pauloensis snake venom. J. Biochem., v. 157, p. 137-149, 2015. GOMES, M. S. R.; QUEIROZ, M. R.; MAMEDE, C. C. N.; MENDES, M. M.; HAMAGUCHI, A.; HOMSI-BRANDEBURGO, M. I.; SOUSA, M. V.; AQUINO, E. N.; CASTRO, M. S.; OLIVEIRA, F.; RODRIGUES, V. M. Purification and functional characterization of a new metalloproteinase (BleucMP) from Bothrops leucurus snake venom. Comp. Biochem. Physiol. C, v. 153, p. 290-300, 2011. G?MIS-RUTH, F. X. Structural aspects of the Metzincin Clan of Metalloendopeptidases.Molecular Biotechnology, v. 24, p.157 ? 2002, 2003. GOMIS-R?TH, F.X. Catalytic domain architecture of metzincin metalloproteases. The Journal Biological Chemistry, v. 23, p. 15353-15357, 2009. G?MIS-RUTH, F.X.; BOTELHO, T.O; BODE, W. A stadad orientation for metallopeptidases. Biochimica et Biophysica Acta, v. 1824, p. 157-163, 2012. GOMIS-RUTH, F. X.; MEYER, E. F.; KRESS, L. F.; POLITI, V. Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors. Protein Sci., v. 7, p. 283-292, 1998. GONG, W.; ZHU, X.; LIU, S.; TENG, M.; NIU, L. Crystal structures of acutolysin A, a three-disulfide hemorrhagic zing metalloproteinase from the snake venom of Agkistrodon acutus. Journal Mol. Biol., v. 283, p. 657-668, 1998. GOUJON, M.; MCWILLIAM, H.; LI, W.; VALENTIN, F.; SQUIZZATO, S.; PAERN, J.; LOPEZ, R. A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Research, v. 38, p. 695-699, 2010. GRAMS, R.; HUBER, R.; KRESS, L. F.; MORODER, L.; BODE, W. Activation of snake venom metalloproteinase by a cysteine switch-like mechanism. Federation of European Biochemical Societies FEBS Letters, v. 335, p. 76-80, 1993. GUEX, N.; PEITSCH, M. C. Swiss-Model and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis, v. 18, p. 2714-2723, 1997. GUEX, N.; PEITSCH, M. C.; SCHWEDE, T. Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective. Electrophoresis, v. 30, p. 162-173, 2009. GUTIERREZ, J. M.; LOMONTE, B. 2003. Efectos locales en el envenenamento of?dico em Am?rica Latina, p. 310-323. In: CARDOSO, J. L. C.; FRAN?A, F. O. S.; WEN, F. H.; M?LAQUE, C. M. S.; HADDAD-JR. Animais pe?onhentos no Brasil: biologia, cl?nica e terap?utica dos acidentes. S?o Paulo: Savier, FAPESP, 480 p. GUTI?RREZ, J. M.; OWNBY, C. L. Skeletal muscle degeneration induced by venom phospholipases A2: insights into the mechanisms of local and systemic myotoxicity. Toxicon, v. 42, p. 915?931, 2003. 71 GUTIERREZ, J.M.; RUCAVADO, A.; ESCALANTE, T.; DIAZ, C. Hemorrhage induced by snake venom metalloproteinases: biochemical and biophysical mechanisms involved in microvessel damage. Toxicon, v. 45, p. 997-1011, 2005. GUTI?RREZ, J. M.; RUCAVADO, A. Snake venom metalloproteinases: Their role the pathogenesis of local tissue damage. Biochimie, v. 82, p. 841 ? 850 , 2000. GUTI?RREZ, J. M.; LOMONTE, B.; L?ON, G.; ALAPE-GIR?N, A.; FLOREZ-D?AZ, M.; SANZ, L.; ?NGULO, Y.; CALVETE, J. J. Snake venomics and antivenomics: Proteomic tools in the design and controlo f antivenoms for the treatment of snakebite envenoming. Journal of Proteomics, v. 72, p. 165-182, 2009a. GUTI?RREZ, J. M.; RUCAVADO, A.; CHAVES, F.; D?AZ, C.; ESCALANTE, T. Experimental pathology of local tissue damage induced by Bothrops asper snake venom. Toxicon, v. 54, p. 958-975, 2009b. GUTI?RREZ, J. M.; RUCAVADO, A.; ESCALANTE, T.; LOMONTE, B.; ?NGULO, Y. Tissue pathology induced by snake venoms: How to unsdertand a complex pattern of alteratios from a systems biology perpective?. Toxicon, v. 55, p. 166-170, 2010. GUTI?RREZ, J. M.; WATTELL. D. A.; WILLIAMS, D. J.; JENSEN, S.; BROWN, N.; CALVETE, J. J.; HARRISON, R. A. The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: The way forward. PLOS Neglected tropical Diseases, v. 7, p. 1-3, 2013. GUTIERREZ, J. M.; WARRELL, D. A.; WILLIAMA, D. J.; JENSEN, S.; BROWN, N.; CALVETE, J. J.; HARRISON, R. A. The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: The way forward. PLoS Negl. Trop. Dis., v. 7, p. 1-3, 2015. HEGE, T. E.; BAUMANN, U. The conserved methionine residue of the metzincins: a sitedirected mutagenesis study. Journal of Molecular Biology, v. 314, n. 2, p. 181-186, 2001. HERPETOLOGIA, Sociedade Brasileira (SBH). Lista das esp?cies de r?pteis brasileiros. Dispon?vel em: < www.sbherpetologia.org.br/checklist/repteis.htm>. Acessado em 01/2016. HOOPER, N. M. Families of zinc metalloproteases. FEBS Letters, v. 354, p. 1-6, 1994. HOWES, J. M.; THEAKSTON, R. D. G.; LAING, G. D. Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators. Toxicon. v. 49, p. 734-739, 2007. ISBISTER, G. K.; BROWN, S. G.; MacDONALDO, E.; WHITE, J.; CURRIE, B. J. Current use of Australian snake antivenoms and frequency of inmediate-tipe hypersensitivity reactions and anaphylaxis. Medical Journal of Australia, v. 188, p. 473-476, 2008. JANEIRO-CINQUINI, T. R. F.; CARDOSO Jr., R. P; ABE, A. S.; SEGURA, O. P. Agrupamento de serpente do g?nero Bothrops pelos caracteres do hemip?nis (Serpentes: Viperidae). In: CONGRESSO BRASILEIRO DE ZOOLOGIA, 24, 1987, Juiz de Fora. Livro de Resumos XIV Congresso Brasileiro de Zoologia, Juiz de Fora: UFMG, p. 358, 1987. 72 JENSEN, F. Introduction to Computational Chemistry. West Sussex: John Wiley & Sons, 1999, 429 p. JONES, G.; WILLETT, P.; GLEN, R. C. Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation. Journal of Molecular Biology, v. 254, p. 43-53, 1995a. JONES, G.; WILLETT, P.; GLEN, R. C. A genetic algorithm for flexible molecular overlay and pharmacophore elucidation. Journal of Computer-Aided Molecular Design, v. 9, p. 532-549, 1995b. JONES, G.; WILLETT, P.; GLEN, R. C.; LEACH, A. R; TAYLOR, R. Development and validation of a genetic algorithm for flexible docking. Journal of Molecular Biology, v. 267, p. 727-748, 1997. KASHIMA, S.; ROBERTO, P. G.; SOARES, A. M.; ASTOLFI-FILHO, S.; PEREIRA, J. O.; GIULIATI, S.; FARIA-JR., M.; XAVIER, M. A. S.; FONTES, M. R. M.; GIGLIO, J. R.; FRAN?A, S. Analysis of Bothrops jararacussu venomous gland transcriptome focusing on structural and functional aspects: I-gene expression profile of highly expressed phospholipase A2. Biochimie, v. 86, p. 211-219, 2004. KASTURIRATNE, A.; WICKREMASINGHE, A. R.; SILVA, N. de; GUNAWARDENA, N. K.; PATHMESWARAN, A.; PREMARATNA, R.; AVIOLI, L.; LALLOO, D. G.; SILVA, H. J. de. The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Medicine, v. 5, p. 01-14, 2008. KAWAGUCHI, N.; XU, X.; TAJINA, R. ADAM 12 protease induces adipogenesis in transgenic mice. The American Journal of Pathology, v. 160, p. 1895-1903, 2002. KIEFER, F.; ARNOLD, K.; K?NZLI, M.; BORDOLI, L.; SCHWEDE, T. The SWISSMODEL Repository and associated resources. Nucleic Acids Research, v. 37, p. 387-392, 2009. KINI, R. M. Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes. Toxicon, v. 42, p. 827-840, 2003. KINI, R.M.; EVANS, H. J. Structural domains in venom proteins: evidence that metalloproteinases and nonenzymatic platelet aggregation inhibitors (disitegrins) from snake venoms are derived by proteolysis from a common precursor. Toxicon, v. 30, p. 265-293, 1992. KITCHEN, D. B.; DECORNEZ, H.; FURR, J. R.; BAJORATH, J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nature Reviews in Drug Discovery, v. 3, p. 935-949, 2004. KOCHVA, E. The origin of snakes and evolution of the venom apparatus. Toxicon, v. 25, p. 65-106, 1987. 73 KORB, O.; ST?TZLE, T.; EXNER, T.E. Empirical scoring function for advanced proteinligand docking with plants. Journal of Chemical Information and Modeling, v. 49, p. 84-96, 2009. KUNTZ, I. D.; BLANEY, J. M.; OATLEY, S. J.; LANGRIDGE, R.; FERRIN, T. E. A geometric approach to macromolecule-ligand interactions. Journal of Molecular Biology, v. 161, p. 269-288, 1982. LAING, D. G.; CLISSA, P. B.; THEAKSTON, R. D. G.; MOURA, D. A. S.; TAYLOR, M. J. Inflammatory pathogenesis of snake venom metalloprotease-induced skin necrosis. European Journal Immunology, v.33, p 3458-3463, 2003. LARKIN, M. A.; BLACKSHIELDS, G.; BROWN, N. P.; CHENNA, R.; MCGETTIGAN, P. A.; MCWILLIAM, H.; VALENTIN, F.; WALLACE, I. M.; WILM, A.; LOPEZ, R.; THOMPSON, J. D.; GIBSON, T. J.; HIGGINS, D. G. Clustal W and Clustal X version 2.0. Bioinformatics, v. 23, p. 2947-2948, 2007. LEACH, A. R. Molecular Modeling: Principles and Applications. 2?ed. New Jersey: Prentice Hall, 2001, 744 p. LEVINE, I. N. Physical Chemistry. 4?ed. Singapore: McGraw Hill International Editions, 1995, 901 p. LI, W.; COWLEY, A.; ULUDAG, M.; GUR, T.; MCWILLIAM, H.; SQUIZZATO, S.; PARK, Y. M.; BUSO, N.; LOPEZ, R. The EMBL-EBI bioinformatics web and programmatic tools framework. Nucleic Acids Research, v. 43, p. 580-584, 2015. LIEBESCHUETZ, J. W.; COLE, J. C.; KORB, O. Pose prediction and virtual screening performance of GOLD scoring functions in a standardized test. J. Comput. Aided Mol. Des., v. 26, p. 737-748, 2012. LINGOTT, T.; SCHLEBERGER, C.; GUTIERREZ, J. M.; MERFORT, I. High-Resolution crystal structure of the snake venom metalloproteinase BaP1 complexed with a peptidomimetic: Insight into inhibitor bindin. Biochemistry, v. 48, p. 6166-6174, 2009. LOVELL, S. C.; DAVIS, I. W.; ARENDAL, W. B.; BAKKER, P. I. W.; WORD, J. M.; PRISANT, M. G.; RICHARDSON, J. S.; RICHARDSON, D. C. Structure validation by Calpha geometry: phi, psi and C-beta deviation. Proteins: Structure, Function and Genetics, v. 50, p. 437-450, 2012. MACHADO, T. Filogenia molecular das esp?cies de Bothrops do grupo neuwiedi (Serpentes, Viperidae). 2010. p. 26. Disserta??o de Mestrado ? Instituto de Bioci?ncias da Universidade de S?o Paulo, S?o Paulo, 2010. MARKLAND, F. S. Snake venoms and the hemostatic system. Toxicon, v. 36, p. 1749-1800, 1998. MASUDA, S.; MURAKAMI, M.; ISHIKAWA, Y.; ISHII, T.; KUDO, I. Diverse cellular localizations of secretory phospholipase A2 enzymes in several human tissues. Biochimica et Biophysica Acta, n. 1736, p. 200-210, 2005. 74 MATRISIAN, L. M. The matrix degrading metalloproteinases. BioEssay, v. 14, p 455-463, 1992. MATSUI, T.; FUJIMURA, Y.; TITANI, K. Snake venom proteases affecting hemostasis and thrombosis. Biochemica et Biophysica Acta: BBA, v. 1477, 146-156. 2000. MACKERROW, J. H. Human fibroblast collagenase contains an amino acid sequence homologous to the zinc-binding site of Serratia proteases. The Journal of Biological Chemistry, v. 262, p. 5943-5943, 1987. MCWILLIAM, H.; LI, W.; ULUDAG, M.; SQUIZZATO, S.; PARK, Y. M.; BUSO, N.; COWLEY, A. P.; LOPEZ, R. Analysis Tool Web Services from the EMBL-EBI. Nucleic Acids Research, v. 41, p. 597-600, 2013. MENDES, M. M.; VIEIRA, S. A. P. B.; GOMES, M. S. R.; PAULA, V. F.; ALC?NTARA, T. M.; HOMSI-BRANDEBURGO, M. I.; SANTOS, J. I.; MAGRO, A. J.; FONTES, M. R. M.; RODRIGUES, V. M. Triacontyl p-coumarate: Na inhibitor of snake venom metalloproteinases. Phytochemistry, v. 86, p. 72-82, 2013. MOCHIZUKI. S.; OKADA, Y. ADAMs in cancer cell proliferation and progression. Cancer Science, v. 98, p. 521-527, 2007. MOOIJ, W. T. M.; VERDONK, M. L. General and targeted statistical potentials for proteinligand interactions. Proteins: Structure, function and Bioinf., v. 61, p. 272-287, 2005. MORRIS, G. M.; GOODSELL, D. S.; HALLIDAY, R. S.; HUEY, R.; HART, W. E.; BELEW, R. K.; OLSON, A. J. Automated docking using a Lamarckian Genetic Algorithm and an empirical binding free energy function. Journal of Computational Chemistry, v. 19, p. 1639-1662, 1998 MOURA-DA-SILVA, A.M.; BUTERA, D.; TANJONI, I. Importance of snake venom metalloproteinases in cell biology: effects on platelets, inflammatory and endothelial cells. Curr. Pharmaceut. Des. v. 28, p. 2893-2905, 2007. MURPHY, G.; NAGASE, H. Reappraising metaloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nature Clinical Practice Rheumatology, v. 4, 128-135, 2008. NAVES-DE-SOUZA, D. L.; GOMES, M. S. R.; FERREIRA, F. B.; RODRIGUES, R. S.; ACH?, D. C.; RICHARDSON, M.; BORGES, M. H.; RODRIGUES, V. M. Biochemical and enzymatic characterization of BpMP-I, a fibrinogenolytic metalloproteinase isolated from Bothropoides pauloensis snake venom. Comparative Biochemistry and Physiology, Part B, v. 161, p. 102-109, 2012. NEIVA, M.; ARRAES, F. B. M.; SOUZA, J. V.; R?DIS-BAPTISTA, G.; PRIETO-DASILVA, A. R. B.; WALTER, M. E. M. T.; BRIGIDO, M. M.; YZMANE, T.; L?PEZLOZANO, J, L.; ASTOLFI-FILHO, S. Transcriptome analysis of the Amazonian viper 75 Bothrops atrox venom gland using expressed sequence tags (ESTs). Toxicon, v. 53, p. 427- 436, 2009. NIKAI, T.; MORI, N.; KISHIDA, M.; SUGIHARA, H.; TU, A. T. Isolation and biochemical characterization of hemorrhagic toxin from the venom of Crotalus atrox (western diamondback rattlesnake). Arch. Biochem. Biophys., v. 231, p. 309-319, 1984. NUNES, D. C. O.; FRANCO, P. S.; RODRIGUES, V. M.; MENDES, M. M. Aspectos cl?nico-epidemiol?gicos dos acidentes of?dicos ocorridos na regi?o do Tri?gulo Mineiro, Minas Gerais, Brasil: Estudo retrospectivo. Biosci. J., v. 30, p. 1942-1951, 2014. NU?ES, V.; CID, P.; SANZ, L.; TORRE, P. D. L.; ?NGULO, Y.; LOMONTE, B.; GUITI?REZ, J. M.; CALVETE, J. J. Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Per? and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism. Journal of Proteomics, v. 73, p. 57-58, 2009. OLIVEIRA, C. F.; LOPES, D. S.; MENDES, M. M.; HOMSI-BRADEBURGO, M. I.; HAMAGUCHI, A.; ALCANTARA, T. M.; CLISSA, P. B.; RODRIGUES, V. M. Insights of Local Tissue Damage and Regeneration Induced By Bnsp-7, a Myotoxin Isolated from Bothrops (Neuwiedi) Pauloensis Snake Venom. Toxicon, v. 53, p. 560-569, 2009. OLIVEIRA, F. G.; SANT?ANNA, C. M. R.; CAFFARENA, E. R.; DARDENNE, L. E.; BARREIRO, E. J. Molecular docking study and development of na empirical vinding free energy model for phosphodiesterase 4 inhibitors. Bioorganic and Medicinal Chemistry, v. 14, p. 6001-6011, 2006. OLIVEIRA, F. G.; SANT?ANNA, C. M. R.; CAFFARENA, E. R.; DARDENNE, L. E.; OLIVEIRA, F. G. Estudo do perfil de intera??o de fosfodiesterase 4 com seus inibidores. Disserta??o de Mestrado, Instituto de Qu?mica, Universidade Federal do Rio de Janeiro ? RJ, 2005. PAIVA, R. O.; HNEIPP, L. F.; GOULAR, C. M.; ALBUQUERQUE, M. A.; ECHEVARRIA, A. Antifungal activities of thiosemicarbazones and semicarbazones against mycotoxigenic fungi. Ci?nc. Agrotec. Lavras, v. 38, p. 531-537, 2014. PARKINSON, C. L.; CHIPPINDALE, P.; CAMPBELL, J. Multigene analyses of pitviper phylogeny with comments on their biogeographical history. In: SCHUETT, G. W.; HOGGREN, M.; DOUGLAS, M. E.; GREENE, H. W. (Eds.). Biology of the vipers. Utah: Eagle Montain, p. 93-110, 2002. PEARSON, R. G. Hard and Soft acids and bases. J. Am. Chem. Soc., v. 85, p. 3533-3539, 1963. PESANTES, O. S.; FERNANDES, W. Afinidade de Bothrops erythromelas aferida atrav?s da eletroforese do plasma e da morfologia do hemip?nis (Serpentes: Viperidae). In: CONGRESSO BRASILEIRO DE ZOOLOGIA, 26, 1989, Jo?o Pessoa. Livro de Resumos XVI Congresso Brasileiro de Zoologia, Jo?o Pessoa: UFPB, p. 74-75, 1989. POLITI, A.; DURDAGI, S.; MOUTEVELIS-MINAKAKIS, P.; KOKOTOS, G.; MAVROMOUSTAKOS, T. Development of accurate binding affinity predictions of novel 76 renin inhibitors through molecular docking studies. Journal of Mol. Grap. And Modell., v. 29, p. 425-435, 2010. POPOVIC-BIJELIC, A.; KOWOL, C. R.; LIND, M. E.; LUO, J.; HIMO, F.; ENYEDY, E. A.; ARION, V. B.; GRASLUND, A. Ribonucleotide reductase inhibition by metal compleses of triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone): a combined experimental and theoretical study. J. Inorg. Biochem., v. 105, p. 1422-1431, 2011. PRIMAKOFF, P.; MYLES, D.G. Penetration, adhesion, and fusion in mammalian sperm-egg interaction. Science, v. 296, 2183-2185, 2002. QUEIROZ, G. P.; PESSOA, L. A.; PORTARO, F. C. V.; FURTADO, M. F. D.; TAMBOURGI, D. V. Interespecific variation in venom composition and toxicity of Brazilian snakes from Bothrops genus. Toxicon, v. 52, p. 842-851, 2008. RAMACHANDRAN, G. N.; SASISKEHARAN, V. Conformation of polypeptides and proteins. Advances in Protein Chemistry, v. 23, p. 283-256, 1968. RAMOS, O. H. P.; SELISTRE-DE-ARA?JO, H. S. Snake venom metalloprotease-structure and function of catalytic and desintegrin domains. Comparative biochemistry and Physiology ? parte C, v. 142, p. 328-346, 2006. RAWLINGS, N. D.; WALLER, M.; BARRETT, A. J.; BATEMAN, A. MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Research, v. 42, p. 503-509, 2014. ROCHA, G. B.; FREIRE, R. O.; SIMAS, A. M.; STEWART, J. J. RM1: a reparameterization of AM1 for H, C, N, O, P, S, F, Cl, Br, and I. J. Comput. Chem, v. 27, p. 1101-1111, 2006 RODRIGUES, R. S.; IZIDORO, L. F. M.; TEIXEIRA, S. S.; SILVEIRA, L. B.; HAMAGUCHI, A.; HOMSI-BRANDEBURGO, M. I.; SELISTRE-DE-ARAUJO, H. S.; GIGLIO, J. R.; FULY, A. L.; SOARES, A. M.; RODRIGUES, V. M. Isolation and funcional characterization of a new myotoxic acidic phospholipase A2 from Bothrops pauloensis snake venom. Toxicon, v. 50, p. 153-165, 2007. RODRIGUES, R. S.; BOLDRINI-FRAN?A, J.; FONSECA, F. P. P.; DE-LA-TORRE, P.; HENRIQUE-SILVA, F.; SANZ, L.; CALVETE, J. J.; RODRIGUES, V.M. Combined snake venomics and venom gland transcriptomic analysis of Bothropoides pauloensis. Journal of Proteomics, v. 75, p. 2707-2720, 2012. RODRIGUES, V. M.; SOARES, A. M.; MANCIN, A. C.; FONTES, M. R. M.; HOMSIBRANDEBURGO, M. I.; GIGLIO, J. R. Geographic variations in the composition of composition of myotoxins from Bothrops neuwiedi snake venoms: biochemical characterization and biological activity. Comparative Biochem. and Physiol. v. 121, p. 215? 222, 1998. RODRIGUES, V. M.; LOPES, D. S.; CASTANHEIRA, L. E.; GIMENES, S. N. C.; NAVESDE- SOUZA, D. L.; ACHE, D. C.; BORGES, I. P.; YONEYAMA, K. A. G.; RODRIGUES, 77 R. S. Bothrops pauloensis snake venom toxins: The search for new therapeutic models. Cueent Topics in Medicinal Chemistry, v. 15, p. 670-684, 2015. RODRIGUEZ-ARGUELLES, M. C.; BELICCHI, F. M.; GASPARRI, F. G.; PELIZZI, C.; TARASCONI, P.; ALBERTINI, R.; DALL?AGLIO, P. P.; LUNGHI, P.; PINELLI, S. 2,6- diacetylpyridine bis (thiosemicarbazones) zinc complexes: synthesis, structure, and biological activity. J. Inorg. Biochem., v. 15, p. 157-175, 1995. ROGERS, D.W. Computational Chemistry Using the PC. 3?ed. Hoboken, NJ: John Wiley & Sons Inc., 2003. 349p. SANTOS, A. C. S.; SANT?ANNA, C. M. R. 20-hydroxyecdysone receptor ligand domain: 1. A semiempirical study of dibenzoylhydrazines selectivity. Journal of Molecular Structure, v. 585, p. 61-68, 2002. SANTOS-FILHO, O. A.; ALENCASTRO, R. B. Modelagem de prote?nas por homologia. Qu?mica Nova, v. 26, p. 253-259, 2003. SCHALOSKE, R. H.; DENNIS, E. A. The phospholipase A2 superfamily and its group numbering system. Biochimica et Biophysica Acta, v. 1761, p. 1246-1259, 2006. SEARLE, M. S.; WILLIAMS, D. H. The cost of conformational order: entropy changes in molecular associations. Journal of the American Chemical Society, v. 114, p. 10690-10697, 1992. SEARLE, M. S.; WILLIANS, D. H.; GERHARD, U. contributions in the estimation of binding constants: residual motions and consequences for amide-amide hydrogen bond strengths. Journal of the American Chemical Society, v. 114, p. 10697-10704, 1992. SILVA, V.X. da, 2004. The Bothrops neuwiedi complex, p.410-422. In Campbell, J.A. & Lamar, W.W. (ed.). The Venomous Reptiles of the Western Hemisphere. Comstock, Ithaca, London. SILVA, G. R.. Estudo da reativa??o da acetilcolinesterase inibida por organofosforados: an?lise conformacional da mol?cula de HI-6 e simula??o da rea??o de |
Page generated in 0.0062 seconds