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Peptide Helix-Y(12) as Potential Effector for Peroxisome Proliferator-Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of lipids and glucose metabolism, and immune response. Therefore, they have been considered pharmacological targets for treating metabolic diseases, such as dyslipidemia, atherosclerosis, and non-alc...

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Autores principales: Carrillo-Tripp, Mauricio, Reyes, Yair, Delgado-Coello, Blanca, Mas-Oliva, Jaime, Gutiérrez-Vidal, Roxana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122583/
https://www.ncbi.nlm.nih.gov/pubmed/37096195
http://dx.doi.org/10.1155/2023/8047378
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author Carrillo-Tripp, Mauricio
Reyes, Yair
Delgado-Coello, Blanca
Mas-Oliva, Jaime
Gutiérrez-Vidal, Roxana
author_facet Carrillo-Tripp, Mauricio
Reyes, Yair
Delgado-Coello, Blanca
Mas-Oliva, Jaime
Gutiérrez-Vidal, Roxana
author_sort Carrillo-Tripp, Mauricio
collection PubMed
description Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of lipids and glucose metabolism, and immune response. Therefore, they have been considered pharmacological targets for treating metabolic diseases, such as dyslipidemia, atherosclerosis, and non-alcoholic fatty liver disease. However, the available synthetic ligands of PPARs have mild to significant side effects, generating the necessity to identify new molecules that are selective PPAR ligands with specific biological responses. This study aimed to evaluate some components of the atheroprotective and hepatoprotective HB-ATV-8 nanoparticles [the amphipathic peptide Helix-Y(12), thermozeaxanthin, thermozeaxanthin-13, thermozeaxanthin-15, and a set of glycolipids], as possible ligands of PPARs through blind molecular docking. According to the change in free energy upon protein–ligand binding, ∆G(b), thermozeaxanthins show a more favorable interaction with PPARs, followed by Helix-Y(12). Moreover, Helix-Y(12) interacts with most parts of the Y-shaped ligand-binding domain (LBD), surrounding helix 3 of PPARs, and reaching helix 12 of PPARα and PPARγ. As previously reported for other ligands, Tyr314 and Tyr464 of PPARα interact with Helix-Y(12) through hydrogen bonds. Several PPARα's amino acids are involved in the ligand binding by hydrophobic interactions. Furthermore, we identified additional PPARs' amino acids interacting with Helix-Y(12) through hydrogen bonds still not reported for known ligands. Our results show that, from the studied ligand set, the Helix-Y(12) peptide and Tzeaxs have the most significant probability of binding to the PPARs' LBD, suggesting novel ligands for PPARs.
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spelling pubmed-101225832023-04-23 Peptide Helix-Y(12) as Potential Effector for Peroxisome Proliferator-Activated Receptors Carrillo-Tripp, Mauricio Reyes, Yair Delgado-Coello, Blanca Mas-Oliva, Jaime Gutiérrez-Vidal, Roxana PPAR Res Research Article Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of lipids and glucose metabolism, and immune response. Therefore, they have been considered pharmacological targets for treating metabolic diseases, such as dyslipidemia, atherosclerosis, and non-alcoholic fatty liver disease. However, the available synthetic ligands of PPARs have mild to significant side effects, generating the necessity to identify new molecules that are selective PPAR ligands with specific biological responses. This study aimed to evaluate some components of the atheroprotective and hepatoprotective HB-ATV-8 nanoparticles [the amphipathic peptide Helix-Y(12), thermozeaxanthin, thermozeaxanthin-13, thermozeaxanthin-15, and a set of glycolipids], as possible ligands of PPARs through blind molecular docking. According to the change in free energy upon protein–ligand binding, ∆G(b), thermozeaxanthins show a more favorable interaction with PPARs, followed by Helix-Y(12). Moreover, Helix-Y(12) interacts with most parts of the Y-shaped ligand-binding domain (LBD), surrounding helix 3 of PPARs, and reaching helix 12 of PPARα and PPARγ. As previously reported for other ligands, Tyr314 and Tyr464 of PPARα interact with Helix-Y(12) through hydrogen bonds. Several PPARα's amino acids are involved in the ligand binding by hydrophobic interactions. Furthermore, we identified additional PPARs' amino acids interacting with Helix-Y(12) through hydrogen bonds still not reported for known ligands. Our results show that, from the studied ligand set, the Helix-Y(12) peptide and Tzeaxs have the most significant probability of binding to the PPARs' LBD, suggesting novel ligands for PPARs. Hindawi 2023-04-15 /pmc/articles/PMC10122583/ /pubmed/37096195 http://dx.doi.org/10.1155/2023/8047378 Text en Copyright © 2023 Mauricio Carrillo-Tripp et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Carrillo-Tripp, Mauricio
Reyes, Yair
Delgado-Coello, Blanca
Mas-Oliva, Jaime
Gutiérrez-Vidal, Roxana
Peptide Helix-Y(12) as Potential Effector for Peroxisome Proliferator-Activated Receptors
title Peptide Helix-Y(12) as Potential Effector for Peroxisome Proliferator-Activated Receptors
title_full Peptide Helix-Y(12) as Potential Effector for Peroxisome Proliferator-Activated Receptors
title_fullStr Peptide Helix-Y(12) as Potential Effector for Peroxisome Proliferator-Activated Receptors
title_full_unstemmed Peptide Helix-Y(12) as Potential Effector for Peroxisome Proliferator-Activated Receptors
title_short Peptide Helix-Y(12) as Potential Effector for Peroxisome Proliferator-Activated Receptors
title_sort peptide helix-y(12) as potential effector for peroxisome proliferator-activated receptors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122583/
https://www.ncbi.nlm.nih.gov/pubmed/37096195
http://dx.doi.org/10.1155/2023/8047378
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