|[PLOS ONE] Discovery of a novel potent peptide agonist to adiponectin receptor 1|
|작성자 : 관리자(email@example.com) 작성일 : 18.06.19 조회수 : 73|
|첨부파일 : journal.pone.0199256.pdf|
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 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.
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출처 : PLOS l ONE