DNA-oxaliplatin adduct (Pt-DNA adduct) (Pt-DNA adduct)

DNA-oxaliplatin adducts are the primary cytotoxic lesions formed by the covalent binding of the platinum-based chemotherapeutic agent oxaliplatin to genomic DNA [PMID: 12105103]. These adducts are characterized by a 1,2-diaminocyclohexane (DACH) carrier ligand, which creates a bulkier and more hydrophobic lesion compared to those formed by cisplatin [PMID: 11479610]. The most common forms are 1,2-intrastrand crosslinks between adjacent guanine bases, which significantly distort the DNA double helix and obstruct the progression of DNA and RNA polymerases [PMID: 15151957]. This physical blockade inhibits DNA replication and transcription, ultimately triggering the DNA damage response and programmed cell death [PMID: 12105103]. Notably, the bulky DACH group prevents the recognition of these adducts by the mismatch repair (MMR) system, which explains oxaliplatin's efficacy in certain MMR-deficient tumors that are resistant to other platinum drugs [PMID: 11479610]. Clinically, the formation and persistence of these adducts are the key determinants of oxaliplatin's therapeutic index in treating colorectal and other gastrointestinal malignancies [PMID: 15151957].

Other names

Oxaliplatin-DNA adductDACH-platinum-DNA adduct1,2-diaminocyclohexane platinum-DNA adductPlatinum-DNA crosslink

Oxaliplatin forms reactive platinum complexes that create covalent intra-strand and inter-strand DNA crosslinks, which distort the DNA helix and trigger apoptosis [PubChem, PMID: 12105103].