PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , |
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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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 |
|
_version_ |
1808129322068738048 |