PloS one, 2018-06, Vol.13 (6), p.e0199256-e0199256
2018
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Discovery of a novel potent peptide agonist to adiponectin receptor 1
- Ist Teil von
- PloS one, 2018-06, Vol.13 (6), p.e0199256-e0199256
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0199256Titel-ID: cdi_plos_journals_2056768829
- Format
- –
- Schlagworte
- Adiponectin, Adiponectin - agonists, Adiponectin - chemistry, Agonists (Biochemistry), Biological activity, Biological analysis, Biology and Life Sciences, Biomimetics, Blood Glucose, Cancer therapies, Chemical compounds, Crystal structure, Diabetes, Diabetes mellitus, Diabetes Mellitus, Type 2 - blood, Diabetes Mellitus, Type 2 - drug therapy, Diabetes Mellitus, Type 2 - pathology, Docking, Drug screening, Drug therapy, Fatty acids, Fatty Acids - antagonists & inhibitors, Fatty Acids - chemistry, Foaming agents, Gene expression, Genetic aspects, Glucose metabolism, Health aspects, Humans, Hyperglycemia, In vivo methods and tests, Insulin, Insulin Resistance, Kinases, Medicine and Health Sciences, Metabolic disorders, Metabolism, Molecular Docking Simulation, Obesity, Oxidation, Oxidation-Reduction, Peptides, Peptides - chemistry, Peptides - therapeutic use, Pharmacology, Physical Sciences, Protein Interaction Maps, Proteins, Receptors, Receptors, Adiponectin - agonists, Receptors, Adiponectin - chemistry, Receptors, Adiponectin - therapeutic use, Research and Analysis Methods, Screening, Signal transduction, Signal Transduction - drug effects, Solubility, Sugar, Surface Plasmon Resonance