Autor(es): 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]
Data: 2022
Identificador Persistente: http://hdl.handle.net/11449/233815
Origem: Oasisbr
Assunto(s): Bioactive peptides; Cholesterol; Concentration–response effect; HMGCoAR inhibitor; Molecular docking
Made available in DSpace on 2022-05-01T10:35:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01
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 Bahia
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.
Institute of Chemistry São Paulo State University UNESP, Rua Prof. Francisco Degni
School of Pharmacy Federal University of Bahia, Barão de Jeremoabo Street
Institute of Chemistry São Paulo State University UNESP, Rua Prof. Francisco Degni
CAPES: 11671/2015
FAPESP: 2013/07600-3
FAPESP: 2014/50926-0
CNPq: 301975/2018-3
CNPq: 426235/2016-9
Fundação de Amparo à Pesquisa do Estado da Bahia: BOL0111/2020
Fundação de Amparo à Pesquisa do Estado da Bahia: BOL1867/2018
Fundação de Amparo à Pesquisa do Estado da Bahia: BOL2006/2019
