In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol
Phlorotannins are polyphenolic compounds in marine alga, especially the brown algae. Among numerous phlorotannins, dieckol and phlorofucofuroeckol-A (PFF-A) are the major ones and despite a wider biological activity profile, knowledge of the G protein-coupled receptor (GPCR) targets of these phlorot...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/19/6/326 |
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| author | Pradeep Paudel Su Hui Seong Se Eun Park Jong Hoon Ryu Hyun Ah Jung Jae Sue Choi |
| author_facet | Pradeep Paudel Su Hui Seong Se Eun Park Jong Hoon Ryu Hyun Ah Jung Jae Sue Choi |
| author_sort | Pradeep Paudel |
| collection | DOAJ |
| description | Phlorotannins are polyphenolic compounds in marine alga, especially the brown algae. Among numerous phlorotannins, dieckol and phlorofucofuroeckol-A (PFF-A) are the major ones and despite a wider biological activity profile, knowledge of the G protein-coupled receptor (GPCR) targets of these phlorotannins is lacking. This study explores prime GPCR targets of the two phlorotannins. In silico proteocheminformatics modeling predicted twenty major protein targets and in vitro functional assays showed a good agonist effect at the α2C adrenergic receptor (α<sub>2C</sub>AR) and an antagonist effect at the adenosine 2A receptor (A<sub>2A</sub>R), δ-opioid receptor (δ-OPR), glucagon-like peptide-1 receptor (GLP-1R), and 5-hydroxytryptamine 1A receptor (5-TH<sub>1A</sub>R) of both phlorotannins. Besides, dieckol showed an antagonist effect at the vasopressin 1A receptor (V<sub>1A</sub>R) and PFF-A showed a promising agonist effect at the cannabinoid 1 receptor and an antagonist effect at V<sub>1A</sub>R. In silico molecular docking simulation enabled us to investigate and identify distinct binding features of these phlorotannins to the target proteins. The docking results suggested that dieckol and PFF-A bind to the crystal structures of the proteins with good affinity involving key interacting amino acid residues comparable to reference ligands. Overall, the present study suggests α<sub>2C</sub>AR, A<sub>2A</sub>R, δ-OPR, GLP-1R, 5-TH<sub>1A</sub>R, CB<sub>1</sub>R, and V<sub>1A</sub>R as prime receptor targets of dieckol and PFF-A. |
| first_indexed | 2024-03-10T10:42:56Z |
| format | Article |
| id | doaj.art-652dc28bbe694f2bb9e138717ec148a9 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T10:42:56Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-652dc28bbe694f2bb9e138717ec148a92023-11-21T22:47:49ZengMDPI AGMarine Drugs1660-33972021-06-0119632610.3390/md19060326In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and DieckolPradeep Paudel0Su Hui Seong1Se Eun Park2Jong Hoon Ryu3Hyun Ah Jung4Jae Sue Choi5Department of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 02447, KoreaDepartment of Food Science and Human Nutrition, Jeonbuk National University, Jeonju 54896, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaPhlorotannins are polyphenolic compounds in marine alga, especially the brown algae. Among numerous phlorotannins, dieckol and phlorofucofuroeckol-A (PFF-A) are the major ones and despite a wider biological activity profile, knowledge of the G protein-coupled receptor (GPCR) targets of these phlorotannins is lacking. This study explores prime GPCR targets of the two phlorotannins. In silico proteocheminformatics modeling predicted twenty major protein targets and in vitro functional assays showed a good agonist effect at the α2C adrenergic receptor (α<sub>2C</sub>AR) and an antagonist effect at the adenosine 2A receptor (A<sub>2A</sub>R), δ-opioid receptor (δ-OPR), glucagon-like peptide-1 receptor (GLP-1R), and 5-hydroxytryptamine 1A receptor (5-TH<sub>1A</sub>R) of both phlorotannins. Besides, dieckol showed an antagonist effect at the vasopressin 1A receptor (V<sub>1A</sub>R) and PFF-A showed a promising agonist effect at the cannabinoid 1 receptor and an antagonist effect at V<sub>1A</sub>R. In silico molecular docking simulation enabled us to investigate and identify distinct binding features of these phlorotannins to the target proteins. The docking results suggested that dieckol and PFF-A bind to the crystal structures of the proteins with good affinity involving key interacting amino acid residues comparable to reference ligands. Overall, the present study suggests α<sub>2C</sub>AR, A<sub>2A</sub>R, δ-OPR, GLP-1R, 5-TH<sub>1A</sub>R, CB<sub>1</sub>R, and V<sub>1A</sub>R as prime receptor targets of dieckol and PFF-A.https://www.mdpi.com/1660-3397/19/6/326phhlorotanninsGPCRsagonistantagonistdieckolPFF-A |
| spellingShingle | Pradeep Paudel Su Hui Seong Se Eun Park Jong Hoon Ryu Hyun Ah Jung Jae Sue Choi In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol Marine Drugs phhlorotannins GPCRs agonist antagonist dieckol PFF-A |
| title | In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol |
| title_full | In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol |
| title_fullStr | In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol |
| title_full_unstemmed | In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol |
| title_short | In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol |
| title_sort | in vitro and in silico characterization of g protein coupled receptor gpcr targets of phlorofucofuroeckol a and dieckol |
| topic | phhlorotannins GPCRs agonist antagonist dieckol PFF-A |
| url | https://www.mdpi.com/1660-3397/19/6/326 |
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