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

Autor(es)

da Silva, Jaff Ribeiro ^{[1, 2]} ; de Cerqueira e Silva, Mariana Barros ^[2] ; Philadelpho, Biane Oliveira ^[1] ; de Souza, Victoria Cruz ^[1] ; Machado dos Santos, Johnnie Elton ^[1] ; Castilho, Marcelo Santos ^[1] ; Ferreira, Ederlan de Souza ^[1] ; Cilli, Eduardo Maffud ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Bahia, Sch Pharm, Barao de Jeremoabo St, BR-40170115 Salvador, BA - Brazil

^[2] Sao Paulo State Univ, Inst Chem, UNESP, Rua Prof Francisco Degni, BR-14800060 Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FOOD BIOSCIENCE; v. 44, n. B DEC 2021.
• Citações Web of Science: 0

Resumo

Two newly designed peptides, Pyr-GF and GSTLN, enhance pravastatin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCoAR). In silica experiments have demonstrated the interaction of these peptides with the catalytic and NADPH sites of HMGCoAR. In vitro, the Pyr-GF (IC50 = 117.4 mu M) and GSTLN (IC50 = 278.1 mu M) 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 mu M. 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. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/50926-0 - INCT 2014: biodiversidade e produtos naturais
• Beneficiário: Vanderlan da Silva Bolzani
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático