Nucleophilic biomolecules

Nucleophilic biomolecules represent a diverse class of cellular components characterized by the presence of electron-rich functional groups, such as the thiol groups in cysteine, amino groups in lysine, and various nitrogen and oxygen atoms within DNA bases [PubMed: PMC2675412]. These molecules are essential for maintaining cellular structure, genetic integrity, and metabolic homeostasis. In pharmacology, they are primarily recognized as the targets for electrophilic drugs, particularly alkylating agents and platinum-based compounds used in oncology [National Cancer Institute]. These drugs form covalent bonds with nucleophilic sites, such as the N7 position of guanine in DNA, which results in DNA cross-linking, inhibition of replication, and the induction of apoptosis in cancer cells [StatPearls: Alkylating Agents]. Beyond DNA, small nucleophilic molecules like glutathione play a vital role in detoxifying reactive drug metabolites, thereby protecting the cell from oxidative stress and chemical damage [PubChem]. However, the non-specific reactivity of many electrophilic drugs toward various nucleophilic biomolecules in healthy tissues is a major source of systemic toxicity and secondary malignancies [PubMed: PMC4707116].

Other names

Cellular nucleophilesNucleophilic targetsNucleophilic cellular components

Covalent modification of nucleophilic sites (alkylation or arylation) leading to DNA cross-linking, strand breaks, or protein dysfunction [StatPearls: Alkylating Agents].