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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 12
Affiliation:
[1] Sao Paulo State Univ, Chem Inst, BR-14800900 Araraquara, SP - Brazil
[2] Univ Fed Bahia, Sch Pharm, BR-40170115 Salvador, BA - Brazil
Total Affiliations: 2
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