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

Author(s):Show less -

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]

Affiliation

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

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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 20 OCT 2021.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC