Nucleophilic groups in polymers and macromolecules

Nucleophilic groups in polymers and macromolecules represent electron-rich chemical moieties, such as amino, thiol, and hydroxyl groups, found within biological polymers like DNA and proteins (Berg et al., Biochemistry). These groups are essential for physiological processes, including enzymatic catalysis and the maintenance of structural integrity in cellular components. In pharmacology, these sites are the primary targets for electrophilic drugs, most notably alkylating agents used in cancer therapy (Goodman & Gilman's The Pharmacological Basis of Therapeutics). These drugs form covalent adducts with nucleophilic centers, such as the N7 position of guanine in DNA, to induce cross-linking and trigger apoptosis (National Cancer Institute). However, the ubiquitous nature of these nucleophilic groups across all cellular components presents a major therapeutic challenge. Non-specific reactivity often leads to systemic toxicity, mutagenicity, and the risk of secondary malignancies.

Other names

Biological nucleophilesNucleophilic sitesReactive functional groupsEndogenous nucleophiles

Covalent modification via nucleophilic attack on electrophilic drug centers, leading to DNA alkylation or protein adduct formation.