Exposed nucleophilic groups in microbial proteins and nucleic acids

Exposed nucleophilic groups in microbial proteins and nucleic acids represent a broad class of chemical targets for non-specific antimicrobial agents, including disinfectants and sterilants (McDonnell & Russell, 1999, Clinical Microbiology Reviews). These groups, such as sulfhydryl (-SH), amino (-NH2), and hydroxyl (-OH) moieties, are essential components of enzymes and structural proteins, as well as the nitrogenous bases in DNA and RNA (PubChem, 2024). When targeted by electrophilic agents like glutaraldehyde or ethylene oxide, these nucleophilic sites undergo covalent modification, such as alkylation or cross-linking, which irreversibly inactivates microbial machinery (NIH, StatPearls). This disruption halts critical biological functions, including metabolic catalysis and genetic replication, leading to rapid microbial death. Because these nucleophilic groups are common to both pathogens and host cells, drugs targeting them often lack selectivity, necessitating their use primarily as topical antiseptics or environmental disinfectants to avoid systemic toxicity (ScienceDirect, 2023).

Other names

Microbial nucleophilic sitesNucleophilic moieties in microorganismsReactive groups in microbial macromolecules

Covalent modification (alkylation, oxidation, or cross-linking) of nucleophilic functional groups (e.g., -SH, -NH2, -OH) leading to the inactivation of essential microbial proteins and the degradation of genetic material.