title: A potent peptide as adiponectin receptor 1 agonist to against fibrosis.
abstract: Fibrotic diseases have become a major cause of death in the developed world. AdipoR1 agonists are potent inhibitors of fibrotic responses. Here, we focused on the in silico identification of novel AdipoR1 peptide agonists. A homology model was constructed to predict the 3D structure of AdipoR1. By docking to known active peptides, the putative active site of the model was further explored. A virtual screening study was then carried out with a set of manually designed peptides using molecular docking. Peptides with high docking scores were then evaluated for their anti-fibrotic properties. The data indicated that the novel peptide Pep70 significantly inhibited the proliferation of hepatic stellate cells (HSC) and NIH-3T3 cells (18.33% and 27.80%) and resulted in favouring cell-cycle arrest through increasing the accumulation of cells in the G0/G1 phase by 17.08% and 15.86%, thereby reducing the cell population in the G2/M phase by 11.25% and 15.95%, respectively. Additionally, Pep70 exhibited the most marked suppression on the expression of α-smooth muscle actin (α-SMA), collagen type I alpha1 (COL1A1) and TGF-β1. Therefore, the peptide Pep70 was ultimately identified as an inhibitor of fibrotic responses and as a potential AdipoR1 agonist.
authors.affiliation: a Department of Medicinal Chemistry , School of Pharmacy, China Pharmaceutical University , Nanjing , China.|b School of Life Science and Technology , China Pharmaceutical University , Nanjing , China.
authors.forename: Lingman
authors.initials: L
authors.lastname: Ma
authors.affiliation: a Department of Medicinal Chemistry , School of Pharmacy, China Pharmaceutical University , Nanjing , China.|c Department of Pharmacy , First People's Hospital of Changde City , Changde , Hunan , China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: b School of Life Science and Technology , China Pharmaceutical University , Nanjing , China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Xue
authors.affiliation: b School of Life Science and Technology , China Pharmaceutical University , Nanjing , China.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Wan
authors.affiliation: b School of Life Science and Technology , China Pharmaceutical University , Nanjing , China.
authors.forename: Boping
authors.initials: B
authors.lastname: Ye
authors.affiliation: a Department of Medicinal Chemistry , School of Pharmacy, China Pharmaceutical University , Nanjing , China.
authors.forename: Kejiang
authors.initials: K
authors.lastname: Lin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D041681:NIH 3T3 Cells; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D054419:Receptors, Adiponectin / Q000819:agonists*; D017386:Sequence Homology, Amino Acid; D053773:Transforming Growth Factor beta1 / Q000819:agonists / Q000378:metabolism
chemical_list: D009842:Oligopeptides; C000617552:Pep70 peptide; D010455:Peptides; D054419:Receptors, Adiponectin; D053773:Transforming Growth Factor beta1
keywords: adiponectin receptor 1; anti-fibrotic activity; homology modelling; molecular docking; virtual screening