Discovery of a novel potent peptide agonist to adiponectin receptor 1.
Activation of adiponectin receptors (AdipoRs) by its natural ligand, adiponectin has been known to be involved in modulating critical metabolic processes such as glucose metabolism and fatty acid oxidation as demonstrated by a number of in vitro and in vivo studies over last two decades. These findi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6005460?pdf=render |
| _version_ | 1818385985579253760 |
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| author | Sunghwan Kim Younho Lee Jun Woo Kim Young-Jin Son Min Jung Ma Jee-Hyun Um Nam Doo Kim Sang Hyun Min Dong Il Kim Brian B Kim |
| author_facet | Sunghwan Kim Younho Lee Jun Woo Kim Young-Jin Son Min Jung Ma Jee-Hyun Um Nam Doo Kim Sang Hyun Min Dong Il Kim Brian B Kim |
| author_sort | Sunghwan Kim |
| collection | DOAJ |
| description | Activation of adiponectin receptors (AdipoRs) by its natural ligand, adiponectin has been known to be involved in modulating critical metabolic processes such as glucose metabolism and fatty acid oxidation as demonstrated by a number of in vitro and in vivo studies over last two decades. These findings suggest that AdipoRs' agonists could be developed into a potential therapeutic agent for metabolic diseases, such as diabetes mellitus, especially for type II diabetes, a long-term metabolic disorder characterized by high blood sugar, insulin resistance, and relative lack of insulin. Because of limitations in production of biologically active adiponectin, adiponectin-mimetic AdipoRs' agonists have been suggested as alternative ways to expand the opportunity to develop anti-diabetic agents. Based on crystal structure of AdipoR1, we designed AdipoR1's peptide agonists using protein-peptide docking simulation and screened their receptor binding abilities and biological functions via surface plasmon resonance (SPR) and biological analysis. Three candidate peptides, BHD1028, BHD43, and BHD44 were selected and confirmed to activate AdipoR1-mediated signal pathways. In order to enhance the stability and solubility of peptide agonists, candidate peptides were PEGylated. PEGylated BHD1028 exhibited its biological activity at nano-molar concentration and could be a potential therapeutic agent for the treatment of diabetes. Also, SPR and virtual screening techniques utilized in this study may potentially be applied to other peptide-drug screening processes against membrane receptor proteins. |
| first_indexed | 2024-12-14T03:46:51Z |
| format | Article |
| id | doaj.art-0cae4df35cc74e369a187cd0a67e679b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T03:46:51Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0cae4df35cc74e369a187cd0a67e679b2022-12-21T23:18:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019925610.1371/journal.pone.0199256Discovery of a novel potent peptide agonist to adiponectin receptor 1.Sunghwan KimYounho LeeJun Woo KimYoung-Jin SonMin Jung MaJee-Hyun UmNam Doo KimSang Hyun MinDong Il KimBrian B KimActivation of adiponectin receptors (AdipoRs) by its natural ligand, adiponectin has been known to be involved in modulating critical metabolic processes such as glucose metabolism and fatty acid oxidation as demonstrated by a number of in vitro and in vivo studies over last two decades. These findings suggest that AdipoRs' agonists could be developed into a potential therapeutic agent for metabolic diseases, such as diabetes mellitus, especially for type II diabetes, a long-term metabolic disorder characterized by high blood sugar, insulin resistance, and relative lack of insulin. Because of limitations in production of biologically active adiponectin, adiponectin-mimetic AdipoRs' agonists have been suggested as alternative ways to expand the opportunity to develop anti-diabetic agents. Based on crystal structure of AdipoR1, we designed AdipoR1's peptide agonists using protein-peptide docking simulation and screened their receptor binding abilities and biological functions via surface plasmon resonance (SPR) and biological analysis. Three candidate peptides, BHD1028, BHD43, and BHD44 were selected and confirmed to activate AdipoR1-mediated signal pathways. In order to enhance the stability and solubility of peptide agonists, candidate peptides were PEGylated. PEGylated BHD1028 exhibited its biological activity at nano-molar concentration and could be a potential therapeutic agent for the treatment of diabetes. Also, SPR and virtual screening techniques utilized in this study may potentially be applied to other peptide-drug screening processes against membrane receptor proteins.http://europepmc.org/articles/PMC6005460?pdf=render |
| spellingShingle | Sunghwan Kim Younho Lee Jun Woo Kim Young-Jin Son Min Jung Ma Jee-Hyun Um Nam Doo Kim Sang Hyun Min Dong Il Kim Brian B Kim Discovery of a novel potent peptide agonist to adiponectin receptor 1. PLoS ONE |
| title | Discovery of a novel potent peptide agonist to adiponectin receptor 1. |
| title_full | Discovery of a novel potent peptide agonist to adiponectin receptor 1. |
| title_fullStr | Discovery of a novel potent peptide agonist to adiponectin receptor 1. |
| title_full_unstemmed | Discovery of a novel potent peptide agonist to adiponectin receptor 1. |
| title_short | Discovery of a novel potent peptide agonist to adiponectin receptor 1. |
| title_sort | discovery of a novel potent peptide agonist to adiponectin receptor 1 |
| url | http://europepmc.org/articles/PMC6005460?pdf=render |
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