Design, synthesis, and evaluation of Bothrops venom serine protease peptidic inhibitors

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dc.contributorLEDS - Laboratório de Dor e Sinalizaçãopt_BR
dc.contributorLab. Biologia Molecularpt_BR
dc.contributorLab. Imunoquímicapt_BR
dc.contributor.authorSilva, Gloria Maria dapt_BR
dc.contributor.authorSouza, Daniel Henrique Berto dept_BR
dc.contributor.authorWaitman, Karoline B.pt_BR
dc.contributor.authorEbram, Matteo Celanopt_BR
dc.contributor.authorFessel, Melissa R.pt_BR
dc.contributor.authorZainescu, Iuliu Cezarpt_BR
dc.contributor.authorPortaro, Fernanda Calheta Vieirapt_BR
dc.contributor.authorHeras, Montsept_BR
dc.contributor.authorChudzinski, Sonia Aparecida de Andradept_BR
dc.identifier.citationSilva GM, Souza DHB, Waitman KB., Ebram MC, Fessel MR., Zainescu IC, et al. Design, synthesis, and evaluation of Bothrops venom serine protease peptidic inhibitors. J Venom Anim Toxins Incl Trop Dis. 2021 Jan;27:e20200066. doi:10.1590/1678-9199-jvatitd-2020-0066.pt_BR
dc.description.abstractBackground: In Central and South America, snakebite envenomation is mainly caused by Bothrops spp. snakes, whose venoms feature significant biochemical richness, including serine proteases. The available bothropic antivenoms are efficient in avoiding fatalities, but do not completely neutralize venom serine proteases, which are co-responsible for some disorders observed during envenomation. Methods: In order to search for tools to improve the antivenom’s, 6-mer peptides were designed based on a specific substrate for Bothrops jararaca venom serine proteases, and then synthesized, with the intention to selectively inhibit these enzymes. Results: Using batroxobin as a snake venom serine protease model, two structurally similar inhibitor peptides were identified. When tested on B. jararaca venom, one of the new inhibitors displayed a good potential to inhibit the activity of the venom serine proteases. These inhibitors do not affect human serine proteases as human factor Xa and thrombin, due to their selectivity. Conclusion: Our study identified two small peptides able to inhibit bothropic serine proteases, but not human ones, can be used as tools to enhance knowledge of the venom composition and function. Moreover, one promising peptide (pepC) was identified that can be explored in the search for improving Bothrops spp. envenomation treatment.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorshipFundação Butantanpt_BR
dc.relation.ispartofJournal of Venomous Animals and Toxins Including Tropical Diseasespt_BR
dc.rightsOpen Accesspt_BR
dc.titleDesign, synthesis, and evaluation of Bothrops venom serine protease peptidic inhibitorspt_BR
dc.contributor.externalUniversity of Oxfordpt_BR
dc.contributor.externalUniversity of Gironapt_BR
dc.subject.keywordSnake venompt_BR
dc.subject.keywordSerine proteasept_BR
dc.relation.ispartofabbreviatedJ Venom Anim Toxins Incl Trop Dispt_BR
dc.identifier.citationabntv. 27, e20200066, jan. 2021pt_BR
dc.identifier.citationvancouver2021 Jan;27:e20200066pt_BR
dc.contributor.butantanSilva, Gloria Maria da|:Aluno|:LEDS - Laboratório de Dor e Sinalização|:PrimeiroAutorpt_BR
dc.contributor.butantanSouza, Daniel Henrique Berto de|:Aluno|:LEDS - Laboratório de Dor e Sinalizaçãopt_BR
dc.contributor.butantanEbram, Matteo Celano|:Aluno|:LEDS - Laboratório de Dor e Sinalizaçãopt_BR
dc.contributor.butantanFessel, Melissa R|:Colaborador|:pt_BR
dc.contributor.butantanPortaro, Fernanda Calheta Vieira|:Pesquisador:Docente Permanente PPGTOX|:Lab. Imunoquímicapt_BR
dc.contributor.butantanChudzinski, Sonia Aparecida de Andrade|:Pesquisador:Docente Colaborador PPGTOX|:LEDS - Laboratório de Dor e Sinalização|:Autor de correspondênciapt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2017/04321-7pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/07467-1pt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.sponsorship.butantanFundação Butantanpt_BR
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