Peptide Helix-Y12 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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2023/8047378 |
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| _version_ | 1850158922209427456 |
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| author | Mauricio Carrillo-Tripp Yair Reyes Blanca Delgado-Coello Jaime Mas-Oliva Roxana Gutiérrez-Vidal |
| author_facet | Mauricio Carrillo-Tripp Yair Reyes Blanca Delgado-Coello Jaime Mas-Oliva Roxana Gutiérrez-Vidal |
| author_sort | Mauricio Carrillo-Tripp |
| collection | DOAJ |
| 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-Y12, 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, ∆Gb, thermozeaxanthins show a more favorable interaction with PPARs, followed by Helix-Y12. Moreover, Helix-Y12 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-Y12 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-Y12 through hydrogen bonds still not reported for known ligands. Our results show that, from the studied ligand set, the Helix-Y12 peptide and Tzeaxs have the most significant probability of binding to the PPARs’ LBD, suggesting novel ligands for PPARs. |
| format | Article |
| id | doaj-art-673ffea9174a4ed4b51aba35e3e2a332 |
| institution | OA Journals |
| issn | 1687-4765 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-673ffea9174a4ed4b51aba35e3e2a3322025-08-20T02:23:44ZengWileyPPAR Research1687-47652023-01-01202310.1155/2023/8047378Peptide Helix-Y12 as Potential Effector for Peroxisome Proliferator-Activated ReceptorsMauricio Carrillo-Tripp0Yair Reyes1Blanca Delgado-Coello2Jaime Mas-Oliva3Roxana Gutiérrez-Vidal4Biomolecular Diversity LaboratoryMetabolic Diseases LaboratoryInstituto de Fisiología Celular, Universidad Nacional Autónoma de MéxicoInstituto de Fisiología Celular, Universidad Nacional Autónoma de MéxicoMetabolic Diseases LaboratoryPeroxisome 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-Y12, 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, ∆Gb, thermozeaxanthins show a more favorable interaction with PPARs, followed by Helix-Y12. Moreover, Helix-Y12 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-Y12 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-Y12 through hydrogen bonds still not reported for known ligands. Our results show that, from the studied ligand set, the Helix-Y12 peptide and Tzeaxs have the most significant probability of binding to the PPARs’ LBD, suggesting novel ligands for PPARs.http://dx.doi.org/10.1155/2023/8047378 |
| spellingShingle | Mauricio Carrillo-Tripp Yair Reyes Blanca Delgado-Coello Jaime Mas-Oliva Roxana Gutiérrez-Vidal Peptide Helix-Y12 as Potential Effector for Peroxisome Proliferator-Activated Receptors PPAR Research |
| title | Peptide Helix-Y12 as Potential Effector for Peroxisome Proliferator-Activated Receptors |
| title_full | Peptide Helix-Y12 as Potential Effector for Peroxisome Proliferator-Activated Receptors |
| title_fullStr | Peptide Helix-Y12 as Potential Effector for Peroxisome Proliferator-Activated Receptors |
| title_full_unstemmed | Peptide Helix-Y12 as Potential Effector for Peroxisome Proliferator-Activated Receptors |
| title_short | Peptide Helix-Y12 as Potential Effector for Peroxisome Proliferator-Activated Receptors |
| title_sort | peptide helix y12 as potential effector for peroxisome proliferator activated receptors |
| url | http://dx.doi.org/10.1155/2023/8047378 |
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