IAF, QGF, and QDF Peptides Exhibit Cholesterol-Lowering Activity through a Statin-like HMG-CoA Reductase Regulation Mechanism: In Silico and In Vitro Approach

Autor(es):Mostrar menos -

Silva, Mariana ^{[1, 2]} ; Philadelpho, Biane ^[2] ; Santos, Johnnie ^[2] ; Souza, Victoria ^[2] ; Souza, Caio ^[2] ; Santiago, Victoria ^[2] ; Silva, Jaff ^{[1, 2]} ; Souza, Carolina ^[2] ; Azeredo, Francine ^[2] ; Castilho, Marcelo ^[2] ; Cilli, Eduardo ^[1] ; Ferreira, Ederlan ^[2]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Chem Inst, BR-14800900 Araraquara, SP - Brazil

^[2] Univ Fed Bahia, Sch Pharm, BR-40170115 Salvador, BA - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 20 OCT 2021.
• Citações Web of Science: 1

Resumo

In this study, in silico approaches are employed to investigate the binding mechanism of peptides derived from cowpea beta-vignin and HMG-CoA reductase. With the obtained information, we designed synthetic peptides to evaluate their in vitro enzyme inhibitory activity. In vitro, the total protein extract and < 3 kDa fraction, at 5000 mu g, support this hypothesis (95% and 90% inhibition of HMG-CoA reductase, respectively). Ile-Ala-Phe, Gln-Gly-Phe, and Gln-Asp-Phe peptides were predicted to bind to the substrate binding site of HMGCR via HMG-CoAR. In silico, it was established that the mechanism of HMG-CoA reductase inhibition largely entailed mimicking the interactions of the decalin ring of simvastatin and via H-bonding; in vitro studies corroborated the predictions, whereby the HMG-CoA reductase activity was decreased by 69%, 77%, and 78%, respectively. Our results suggest that Ile-Ala-Phe, Gln-Gly-Phe, and Gln-Asp-Phe peptides derived from cowpea beta-vignin have the potential to lower cholesterol synthesis through a statin-like regulation mechanism.</p> (AU)

• 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
• 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