Exploration into the Antitumor Potential of Chiral Oligopeptides: a Comprehensive Study Encompassing Design, Synthesis, In Silico Target Screening and Experimental Validation

biological activity assays demonstrated that these chiral compounds exhibited potent antitumor effects against human liver cancer BEL-7404 cells, potentially inducing autophagy and apoptosis. The potential targets of the oligopeptides were initially screened using pharmacophore mapping (PharmMapper) in conjunction with reverse molecular docking (GalaxySagittarius-AF), which revealed that poly(ADP-ribose) polymerase 1 (PARP1) is a key target for these compounds. The target was subsequently validated using biolayer interferometry (BLI, dose-response curves), enzyme-linked immunosorbent assay, molecular docking, and molecular dynamics simulations. The quantitative structure-activity relationship (QSAR) of the prepared peptides was analyzed using PaDEL-Descriptor to provide a rational basis for future peptide-based drug design. This study presents a straightforward, cost-effective, and rapid methodology for the chemical synthesis, biological activity validation, and AI-assisted target identification of antitumor chiral linear oligopeptides.