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.

Enzymatic Production, Bioactivity, and Bitterness of Chickpea (Cicer arietinum) Peptides

“…The peptide RQSHFANAQP, mentioned previously as being antioxidant and having hypolipidemic effects, was also found to decrease the viability of cancer cells (Table ). Interestingly, the peptide fragment ANAQ of the peptide RQSHFANAQP was found to favorably interact in silico with the structure of the protein p53, which is heavily involved in cancer signaling (Xue et al., ). More research is needed on the anticarcinogenic effects of chickpea protein hydrolysates and peptides.…”