Identification of Novel Peptides Targeting DNA Methyltransferase 1 (DNMT-1) for Breast Cancer Treatment

Epigenetic alteration shows an essential role in the process of breast cancer cell proliferation and propagation. DNA methyltransferase (DNMT) is responsible for DNA methylation, resulted in the epigenetic silencing of multiple genes. Hence, inhibiting DNMT-1 is a promising way to block uncontrolled DNA methylation. This study aimed to retrieve a potential peptide compound as DNMT-1 inhibitor due to its desirable properties as drug candidate through virtual screening and molecular docking simulation. A total of 51,957 peptide ligands from PubChem database underwent computational pharmacological screening to eliminate compounds with undesired characteristics. Molecular docking simulation was done with generated pharmacophore features, and the potential ligands with good ΔG binding, RMSD value, and molecular interaction were cyclized to increase the bioavailability of the peptides. Cyclic peptide ligands were tested for its interaction with DNMT-1 protein and ADME-Tox properties. From these steps, three cyclic peptide ligands showed desirable characteristics as a new drug candidate for the DNMT1 inhibitor. [Figure not available: see fulltext.]