Discovery of a novel potent peptide agonist to adiponectin receptor 1
| العنوان: | Discovery of a novel potent peptide agonist to adiponectin receptor 1 |
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| المؤلفون: | Sang Hyun Min, Jun Woo Kim, Sunghwan Kim, Dong Il Kim, Brian B. Kim, Jee-Hyun Um, Min Jung Ma, Young-Jin Son, Younho Lee, Nam Doo Kim |
| المصدر: | PLoS ONE PLoS ONE, Vol 13, Iss 6, p e0199256 (2018) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Blood Glucose, Physiology, medicine.medical_treatment, Peptide Hormones, lcsh:Medicine, Pharmacology, Biochemistry, Binding Analysis, 0302 clinical medicine, Endocrinology, Biomimetics, Immune Physiology, Medicine and Health Sciences, Biochemical Simulations, Protein Interaction Maps, Post-Translational Modification, Phosphorylation, Receptor, lcsh:Science, Adiponectin receptor 1, Innate Immune System, Multidisciplinary, Chemistry, Fatty Acids, Ligand (biochemistry), Molecular Docking Simulation, 030220 oncology & carcinogenesis, Physical Sciences, Cytokines, Adiponectin, Receptors, Adiponectin, Oxidation-Reduction, Signal Peptides, Signal Transduction, Research Article, Agonist, medicine.drug_class, Endocrine Disorders, Immunology, Materials Science, Material Properties, Research and Analysis Methods, 03 medical and health sciences, Insulin resistance, Adipokines, medicine, Diabetes Mellitus, Humans, Chemical Characterization, Virtual screening, Insulin, lcsh:R, Biology and Life Sciences, Proteins, Computational Biology, Surface Plasmon Resonance, Molecular Development, Pegylation, medicine.disease, Hormones, 030104 developmental biology, Diabetes Mellitus, Type 2, Solubility, Immune System, Metabolic Disorders, lcsh:Q, Insulin Resistance, Peptides, Developmental Biology |
| الوصف: | 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. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46a52814ce669c4ac11b122a44b57955 https://pubmed.ncbi.nlm.nih.gov/29912982 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....46a52814ce669c4ac11b122a44b57955 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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