Peptidic Compound as DNA Binding Agent: In Silico Fragment-based Design, Machine Learning, Molecular Modeling, Synthesis, and DNA Binding Evaluation

Cancer remains a global burden, with increasing mortality rates. Current cancer treatments involve controlling the transcription of malignant DNA genes, either directly or indirectly. DNA exhibits various structural forms, including the G-quadruplex (G4), a secondary structure in guanine-rich regions. G4 plays a crucial role in cellular processes by regulating gene expression and telomerase function. Researchers have recently identified G4-stabilizing binding agents as promising anti-cancer compounds. Additionally, peptides have emerged as effective anticancer pharmaceuticals due to their ability to form multiple hydrogen bonds, electrostatic interactions, and van der Waals forces. These properties enable peptides to bind to specific areas of DNA chains selectively. However, despite these advancements, designing G4-binding peptides remains challenging due to a lack of comprehensive information.