PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme

Detalhes bibliográficos
Autor(a) principal: da Silva, Jaff Ribeiro [UNESP]
Data de Publicação: 2021
Outros Autores: de Cerqueira e Silva, Mariana Barros [UNESP], Philadelpho, Biane Oliveira, de Souza, Victória Cruz, dos Santos, Johnnie Elton Machado, Castilho, Marcelo Santos, de Souza Ferreira, Ederlan, Cilli, Eduardo Maffud [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.fbio.2021.101451
http://hdl.handle.net/11449/233815
Resumo: Two newly designed peptides, Pyr-GF and GSTLN, enhance pravastatin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCoAR). In silico experiments have demonstrated the interaction of these peptides with the catalytic and NADPH sites of HMGCoAR. In vitro, the Pyr-GF (IC50 = 117.4 μM) and GSTLN (IC50 = 278.1 μM) peptides exhibit dose-dependent inhibition on the HMGCoAR activity, and the effects are more significant than those observed for original peptides obtained from cowpea and adzuki beans. Compared to pravastatin alone, the Pyr-GF/pravastatin combination produced a small decrease (8%) in HMGCoAR activity, whereas the GSTLN/pravastatin combination produced a significant decrease of 41% on HMGCoAR activity. The association between Pyr-GF/GSTLN peptides decreased the IC50 to 71.8 μM. These results suggest their interaction with different sites; Pyr-GF and pravastatin mainly act on the catalytic site and GSTLN on the NADPH site. Hence, the Pyr-GF and GSTLN peptides and their combination exhibit a cholesterol-lowering effect and act as adjuvants upon association with pravastatin.
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spelling PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzymeBioactive peptidesCholesterolConcentration–response effectHMGCoAR inhibitorMolecular dockingTwo newly designed peptides, Pyr-GF and GSTLN, enhance pravastatin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCoAR). In silico experiments have demonstrated the interaction of these peptides with the catalytic and NADPH sites of HMGCoAR. In vitro, the Pyr-GF (IC50 = 117.4 μM) and GSTLN (IC50 = 278.1 μM) peptides exhibit dose-dependent inhibition on the HMGCoAR activity, and the effects are more significant than those observed for original peptides obtained from cowpea and adzuki beans. Compared to pravastatin alone, the Pyr-GF/pravastatin combination produced a small decrease (8%) in HMGCoAR activity, whereas the GSTLN/pravastatin combination produced a significant decrease of 41% on HMGCoAR activity. The association between Pyr-GF/GSTLN peptides decreased the IC50 to 71.8 μM. These results suggest their interaction with different sites; Pyr-GF and pravastatin mainly act on the catalytic site and GSTLN on the NADPH site. Hence, the Pyr-GF and GSTLN peptides and their combination exhibit a cholesterol-lowering effect and act as adjuvants upon association with pravastatin.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado da BahiaInstitute of Chemistry São Paulo State University UNESP, Rua Prof. Francisco DegniSchool of Pharmacy Federal University of Bahia, Barão de Jeremoabo StreetInstitute of Chemistry São Paulo State University UNESP, Rua Prof. Francisco DegniCAPES: 11671/2015FAPESP: 2013/07600-3FAPESP: 2014/50926-0CNPq: 301975/2018-3CNPq: 426235/2016-9Fundação de Amparo à Pesquisa do Estado da Bahia: BOL0111/2020Fundação de Amparo à Pesquisa do Estado da Bahia: BOL1867/2018Fundação de Amparo à Pesquisa do Estado da Bahia: BOL2006/2019Universidade Estadual Paulista (UNESP)Universidade Federal da Bahia (UFBA)da Silva, Jaff Ribeiro [UNESP]de Cerqueira e Silva, Mariana Barros [UNESP]Philadelpho, Biane Oliveirade Souza, Victória Cruzdos Santos, Johnnie Elton MachadoCastilho, Marcelo Santosde Souza Ferreira, EderlanCilli, Eduardo Maffud [UNESP]2022-05-01T10:35:01Z2022-05-01T10:35:01Z2021-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.fbio.2021.101451Food Bioscience, v. 44.2212-43062212-4292http://hdl.handle.net/11449/23381510.1016/j.fbio.2021.1014512-s2.0-85119370425Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFood Bioscienceinfo:eu-repo/semantics/openAccess2022-05-01T10:35:01Zoai:repositorio.unesp.br:11449/233815Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:27:36.059227Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
title PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
spellingShingle PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
da Silva, Jaff Ribeiro [UNESP]
Bioactive peptides
Cholesterol
Concentration–response effect
HMGCoAR inhibitor
Molecular docking
title_short PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
title_full PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
title_fullStr PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
title_full_unstemmed PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
title_sort PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
author da Silva, Jaff Ribeiro [UNESP]
author_facet da Silva, Jaff Ribeiro [UNESP]
de Cerqueira e Silva, Mariana Barros [UNESP]
Philadelpho, Biane Oliveira
de Souza, Victória Cruz
dos Santos, Johnnie Elton Machado
Castilho, Marcelo Santos
de Souza Ferreira, Ederlan
Cilli, Eduardo Maffud [UNESP]
author_role author
author2 de Cerqueira e Silva, Mariana Barros [UNESP]
Philadelpho, Biane Oliveira
de Souza, Victória Cruz
dos Santos, Johnnie Elton Machado
Castilho, Marcelo Santos
de Souza Ferreira, Ederlan
Cilli, Eduardo Maffud [UNESP]
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Universidade Federal da Bahia (UFBA)
dc.contributor.author.fl_str_mv da Silva, Jaff Ribeiro [UNESP]
de Cerqueira e Silva, Mariana Barros [UNESP]
Philadelpho, Biane Oliveira
de Souza, Victória Cruz
dos Santos, Johnnie Elton Machado
Castilho, Marcelo Santos
de Souza Ferreira, Ederlan
Cilli, Eduardo Maffud [UNESP]
dc.subject.por.fl_str_mv Bioactive peptides
Cholesterol
Concentration–response effect
HMGCoAR inhibitor
Molecular docking
topic Bioactive peptides
Cholesterol
Concentration–response effect
HMGCoAR inhibitor
Molecular docking
description Two newly designed peptides, Pyr-GF and GSTLN, enhance pravastatin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCoAR). In silico experiments have demonstrated the interaction of these peptides with the catalytic and NADPH sites of HMGCoAR. In vitro, the Pyr-GF (IC50 = 117.4 μM) and GSTLN (IC50 = 278.1 μM) peptides exhibit dose-dependent inhibition on the HMGCoAR activity, and the effects are more significant than those observed for original peptides obtained from cowpea and adzuki beans. Compared to pravastatin alone, the Pyr-GF/pravastatin combination produced a small decrease (8%) in HMGCoAR activity, whereas the GSTLN/pravastatin combination produced a significant decrease of 41% on HMGCoAR activity. The association between Pyr-GF/GSTLN peptides decreased the IC50 to 71.8 μM. These results suggest their interaction with different sites; Pyr-GF and pravastatin mainly act on the catalytic site and GSTLN on the NADPH site. Hence, the Pyr-GF and GSTLN peptides and their combination exhibit a cholesterol-lowering effect and act as adjuvants upon association with pravastatin.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-01
2022-05-01T10:35:01Z
2022-05-01T10:35:01Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.fbio.2021.101451
Food Bioscience, v. 44.
2212-4306
2212-4292
http://hdl.handle.net/11449/233815
10.1016/j.fbio.2021.101451
2-s2.0-85119370425
url http://dx.doi.org/10.1016/j.fbio.2021.101451
http://hdl.handle.net/11449/233815
identifier_str_mv Food Bioscience, v. 44.
2212-4306
2212-4292
10.1016/j.fbio.2021.101451
2-s2.0-85119370425
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Food Bioscience
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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