A Kunitz-type peptide from Dendroaspis polylepis venom as a simultaneous inhibitor of serine and cysteine proteases

Full metadata record
DC FieldValueLanguage
dc.contributorLaboratório de Imunoquímicapt_BR
dc.contributorLaboratório de Bioquímica e Biofísicapt_BR
dc.contributor.authorKodama, Roberto Tadashipt_BR
dc.contributor.authorKuniyoshi, Alexandre Kazuopt_BR
dc.contributor.authorSilva, Cristiane Castilho Fernandes dapt_BR
dc.contributor.authorCajado-Carvalho, Danielapt_BR
dc.contributor.authorDuzzi, Brunopt_BR
dc.contributor.authorMariano, Douglas Oscar Ceolinpt_BR
dc.contributor.authorPimenta, Daniel Carvalhopt_BR
dc.contributor.authorBorges, Rafaelpt_BR
dc.contributor.authorSilva, Wilmar Dias dapt_BR
dc.contributor.authorPortaro, Fernanda Calheta Vieirapt_BR
dc.date.accessioned2020-10-27T18:08:04Z-
dc.date.available2020-10-27T18:08:04Z-
dc.date.issued2020-
dc.identifier.citationKodama RT, Kuniyoshi AK, Silva CCF, Cajado-Carvalho D, Duzzi B, Mariano DOC, et al. A Kunitz-type peptide from Dendroaspis polylepis venom as a simultaneous inhibitor of serine and cysteine proteases. Journal of Venomous Animals and Toxins Including Tropical Diseases. 2020 Oct;26:e20200037. doi:10.1590/1678-9199-jvatitd-2020-0037.pt_BR
dc.identifier.issn0104-7930-
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3286-
dc.description.abstractBackground: Proteases play an important role for the proper physiological functions of the most diverse organisms. When unregulated, they are associated with several pathologies. Therefore, proteases have become potential therapeutic targets regarding the search for inhibitors. Snake venoms are complex mixtures of molecules that can feature a variety of functions, including peptidase inhibition. Considering this, the present study reports the purification and characterization of a Kunitz-type peptide present in the Dendroaspis polylepis venom as a simultaneous inhibitor of elastase-1 and cathepsin L. Methods: The low molecular weight pool from D. polylepis venom was fractionated in reverse phase HPLC and all peaks were tested in fluorimetric assays. The selected fraction that presented inhibitory activity over both proteases was submitted to mass spectrometry analysis, and the obtained sequence was determined as a Kunitz-type serine protease inhibitor homolog dendrotoxin I. The molecular docking of the Kunitz peptide on the elastase was carried out in the program Z-DOCK, and the program RosettaDock was used to add hydrogens to the models, which were re-ranked using ZRANK program. Results: The fraction containing the Kunitz molecule presented similar inhibition of both elastase-1 and cathepsin L. This Kunitz-type peptide was characterized as an uncompetitive inhibitor for elastase-1, presenting an inhibition constant (Ki) of 8 μM. The docking analysis led us to synthesize two peptides: PEP1, which was substrate for both elastase-1 and cathepsin L, and PEP2, a 30-mer cyclic peptide, which showed to be a cathepsin L competitive inhibitor, with a Ki of 1.96 µM, and an elastase-1 substrate. Conclusion: This work describes a Kunitz-type peptide toxin presenting inhibitory potential over serine and cysteine proteases, and this could contribute to further understand the envenomation process by D. polylepis. In addition, the PEP2 inhibits the cathepsin L activity with a low inhibition constant.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.format.extente20200037pt_BR
dc.languageengpt_BR
dc.publisherCenter for the Study of Venoms and Venomous Animals (CEVAP)pt_BR
dc.relation.ispartofJournal of Venomous Animals and Toxins Including Tropical Diseasespt_BR
dc.rightsOpen Accesspt_BR
dc.titleA Kunitz-type peptide from Dendroaspis polylepis venom as a simultaneous inhibitor of serine and cysteine proteasespt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1590/1678-9199-jvatitd-2020-0037-
dc.identifier.urlhttp://dx.doi.org/10.1590/1678-9199-jvatitd-2020-0037-
dc.contributor.externalUniversidade Estadual Paulista Júlio de Mesquita Filho (UNESP)pt_BR
dc.publisher.cityBotucatupt_BR
dc.identifier.citationvolume26-
dc.subject.keywordDendroaspis polylepis venompt_BR
dc.subject.keywordInhibitorpt_BR
dc.subject.keywordSerine peptidasept_BR
dc.subject.keywordCysteine peptidasept_BR
dc.subject.keywordKunitz-type peptidept_BR
dc.relation.ispartofabbreviatedJournal of Venomous Animals and Toxins Including Tropical Diseasespt_BR
dc.identifier.citationabntv. 26, e20200037, out. 2020-
dc.identifier.citationvancouver2020 Oct;26:e20200037-
dc.publisher.countryBrazilpt_BR
dc.contributor.butantanKodama, Roberto Tadashi|:Aluno|:Laboratório de Imunoquímica|:PrimeiroAutorpt_BR
dc.contributor.butantanKuniyoshi, Alexandre Kazuo|:Aluno|:Laboratório de Imunoquímicapt_BR
dc.contributor.butantanSilva, Cristiane Castilho Fernandes da|:Aluno|:Laboratório de Imunoquímicapt_BR
dc.contributor.butantanCajado-Carvalho, Daniela|:Aluno|:Laboratório de Imunoquímicapt_BR
dc.contributor.butantanDuzzi, Bruno|:Aluno|:Laboratório de Imunoquímicapt_BR
dc.contributor.butantanMariano, Douglas Oscar Ceolin|:Aluno|:Laboratório de Bioquímica e Biofísicapt_BR
dc.contributor.butantanPimenta, Daniel Carvalho|:Pesquisador:Docente permanente PPGTOX|:Laboratório de Bioquímica e Biofísicapt_BR
dc.contributor.butantanDias da Silva, Wilmar|:Pesquisador|:Laboratório de Imunoquímicapt_BR
dc.contributor.butantanPortaro, Fernanda Calheta Vieira|:Pesquisador:Docente permanente PPGTOX|:Laboratório de Imunoquímica|:Autor de correspondênciapt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2015/13124-5pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/ 07467-1pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2011/02061-1pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2015/15364-3pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/15344-7pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦490048/2005-6pt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦23038.000814/2011-83pt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦88882.377116/2019-01pt_BR
dc.identifier.bvsccBR78.1-
dc.identifier.bvsdbIBProd-
item.openairetypeArticle-
item.fulltextSem Texto completo-
item.grantfulltextnone-
crisitem.journal.journalissn#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.journal.journaleissn#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
Appears in Collections:Artigos de periódicos

Show simple item record

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.