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Potential Inhibitors of the Activity of the Cholesterol-Ester Transfer Protein.
Tárraga, Wilson Alberto; Garda, Horacio Alberto; Toledo, Juan Domingo; Gonzalez, Marina Cecilia.
Afiliação
  • Tárraga WA; Institute of Biochemical Research of La Plata Rodolfo Brenner (INIBIOLP), CONICET-CCT La Plata, Faculty of Medical Sciences, National University of La Plata (UNLP), La Plata, Argentina.
  • Garda HA; Institute of Biochemical Research of La Plata Rodolfo Brenner (INIBIOLP), CONICET-CCT La Plata, Faculty of Medical Sciences, National University of La Plata (UNLP), La Plata, Argentina.
  • Toledo JD; Institute of Biochemical Research of La Plata Rodolfo Brenner (INIBIOLP), CONICET-CCT La Plata, Faculty of Medical Sciences, National University of La Plata (UNLP), La Plata, Argentina.
  • Gonzalez MC; Institute of Biochemical Research of La Plata Rodolfo Brenner (INIBIOLP), CONICET-CCT La Plata, Faculty of Medical Sciences, National University of La Plata (UNLP), La Plata, Argentina.
J Comput Biol ; 26(12): 1458-1469, 2019 12.
Article em En | MEDLINE | ID: mdl-31356116
The cholesterol-ester transfer protein (CETP) exchanges lipids between high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs). The excessive transport of lipids from HDLs to LDLs mediated by this protein can cause an alteration in the deposition of lipoproteins onto the arterial walls, thus promoting the development of arteriosclerosis. Different CETP inhibitors have been tested in recent years, but none has been confirmed as being effectively palliative for the disease. We employed in silico databases and molecular docking as a computational method to predict how potential CETP inhibitors could interact with the active site of the CETP protein. Upon previously comparing two computer software packages to determine which generated a greater number of accurate CETP-inhibitor-complex structures, we chose the more appropriate program for our studies. We then abstracted a series of databases of known CETP inhibitors and noninhibitors exhibiting different 50% concentrations of CETP-inhibitory (INH) activity, to generate virtual structures for docking with different combinations of the CETP receptor. From this process, we obtained as the most suitable structure 4F2A_1OB_C_PCW-it accordingly having a greater area under the receiver operating characteristic curve. The molecular docking of known compounds in comparison with the respective conformation of this inhibitor enabled us to obtain ΔGs (in kcal/mol) from which data we made a first exploration of unknown compounds for CETP-INH activity. Thus, the 4F2A_1OB_C_PCW structure was docked with DrugBank-Approved commercial compounds in an extensive database, whose status had already been established from pharmacokinetics and toxicology. In this study, we present a group of potential compounds as CETP-inhibitor candidates.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Transferência de Ésteres de Colesterol Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: J Comput Biol Assunto da revista: BIOLOGIA MOLECULAR / INFORMATICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Transferência de Ésteres de Colesterol Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: J Comput Biol Assunto da revista: BIOLOGIA MOLECULAR / INFORMATICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos