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

Full metadata record
DC FieldValueLanguage
dc.contributorLab. Imunoquímicapt_BR
dc.contributorLab. 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.issued2020pt_BR
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. J. Venom. Anim. Toxins Trop. Dis.. 2020 Oct;26:e20200037. doi:10.1590/1678-9199-jvatitd-2020-0037.pt_BR
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.language.isoEnglishpt_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-2020-0037pt_BR
dc.identifier.urlhttp://dx.doi.org/10.1590/1678-9199-jvatitd-2020-0037pt_BR
dc.contributor.externalUniversidade Estadual Paulista Júlio de Mesquita Filho (UNESP)pt_BR
dc.identifier.citationvolume26pt_BR
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.ispartofabbreviatedJ. Venom. Anim. Toxins Trop. Dis.pt_BR
dc.identifier.citationabntv. 26, e20200037, out. 2020pt_BR
dc.identifier.citationvancouver2020 Oct;26:e20200037pt_BR
dc.contributor.butantanKodama, Roberto Tadashi|:Aluno|:Lab. Imunoquímica|:PrimeiroAutorpt_BR
dc.contributor.butantanKuniyoshi, Alexandre Kazuo|:Aluno|:Lab. Imunoquímicapt_BR
dc.contributor.butantanSilva, Cristiane Castilho Fernandes da|:Aluno|:Lab. Imunoquímicapt_BR
dc.contributor.butantanCajado-Carvalho, Daniela|:Aluno|:Lab. Imunoquímicapt_BR
dc.contributor.butantanDuzzi, Bruno|:Aluno|:Lab. Imunoquímicapt_BR
dc.contributor.butantanMariano, Douglas Oscar Ceolin|:Aluno|:Lab. Biofísicapt_BR
dc.contributor.butantanPimenta, Daniel Carvalho|:Pesquisador:Docente permanente PPGTOX|:Lab. Biofísicapt_BR
dc.contributor.butantanDias da Silva, Wilmar|:Pesquisador|:Lab. Imunoquímicapt_BR
dc.contributor.butantanPortaro, Fernanda Calheta Vieira|:Pesquisador:Docente permanente PPGTOX|:Lab. 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.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.openairetypeArticle-
item.fulltextCom Texto completo-
item.grantfulltextopen-
item.languageiso639-1English-
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.orcid0000-0003-2406-0860-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid0000-0001-5109-3081-
crisitem.author.orcid0000-0002-9582-4699-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.journal.journalissn#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.journal.journaleissn#PLACEHOLDER_PARENT_METADATA_VALUE#-
Appears in Collections:Artigos de periódicos


Files in This Item:

10.1590.1678-9199-jvatitd-2020-0037.pdf
Description:
Size: 2.17 MB
Format: Adobe PDF
View/Open
Show simple item record

The access to the publications deposited in this repository respects the licenses from journals and publishers.