title: CPe-III-S Metabolism in Vitro and in Vivo and Molecular Simulation of Its Metabolites Using a p53-R273H Mutant.
abstract: It was previously found that CPe-III-S, synthesized according to the chickpea peptide CPe-III (RQSHFANAQP), exhibited an antiproliferative effect. The aim of this study was to investigate the antiproliferative mechanism of CPe-III-S. CPe-III-S was treated by pepsin and trypsin in a simulated gastrointestinal digestion environment as well as in an animal experiment. With HPLC-ESI-MS analysis, three peptide fragments of Ser-His, His-Phe, and Ala-Asn-Ala-Gln were identified. Ser-His was the only common product from both in vitro and in vivo environments. The specific bindings between three peptides and p53-R273H were performed by molecular docking, and the molecular dynamic simulation between Ser-His and p53-R273H revealed the stability of the binding complex. The binding free energy of the complex was -12.56 ± 1.03 kcal/mol with a reliable hydrogen bond between the ligand and Thr284 of p53. Ser-His may restore mutant p53-R273H activity or inhibit its binding with a downstream signal. This metabolite is a potential anticancer factor for suppressing cell proliferation.
authors: School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors: Zhaohui
authors: Z
authors: Xue
authors: School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors: Haichao
authors: H
authors: Wen
authors: School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors: Cen
authors: C
authors: Wang
authors: School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors: Lijuan
authors: L
authors: Zhai
authors: School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors: Aiqing
authors: A
authors: Cheng
authors: School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors: Xiaohong
authors: X
authors: Kou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010434:Pepsin A / Q000737:chemistry; D010446:Peptide Fragments / Q000494:pharmacology; D011487:Protein Conformation; D014357:Trypsin / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004151:Dipeptides; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53; C422849:seryl-histidine; C022144:histidylphenylalanine; D014357:Trypsin; D010434:Pepsin A; C054122:alanylglutamine
keywords: CPe-III; Ser-His; molecular docking; molecular dynamics simulation; p53 mutation