Non-specific nucleophilic sites on DNA, RNA, and proteins

Non-specific nucleophilic sites on DNA, RNA, and proteins refer to electron-rich atoms—primarily nitrogen, oxygen, and sulfur—that serve as targets for highly reactive electrophilic compounds (StatPearls, NBK541111). In the context of oncology, these sites are the primary targets for}

Other names

Cellular nucleophilesNucleophilic centersDNA/RNA/Protein nucleophilesElectrophilic targets

Drugs targeting these sites act by forming highly reactive electrophilic intermediates that undergo nucleophilic attack by atoms such as the N7 of guanine in DNA or sulfur in protein cysteine residues (StatPearls, NBK541111). This covalent binding results in DNA adducts, interstrand and intrastrand cross-links, and protein-DNA cross-links, which physically obstruct DNA replication and transcription (PubMed, 1550693). The resulting genomic instability and cellular stress trigger apoptotic pathways, particularly in rapidly dividing cells (PubChem, CID 2907).