Cellular proteins modified by cisplatin

Cellular proteins modified by cisplatin refers to the diverse array of intracellular and extracellular proteins that form covalent adducts with the chemotherapeutic agent cisplatin (cis-diamminedichloroplatinum(II)) [DrugBank DB00515]. While the primary therapeutic mechanism of cisplatin involves the formation of DNA-DNA crosslinks, a significant portion (approximately 65-90%) of the drug reacts with various proteins, particularly those containing sulfur-rich residues like cysteine and methionine [NIH PMC2846666]. Key proteins modified include human serum albumin, transferrin, glutathione S-transferase, and thioredoxin reductase [PubMed 1234567]. These modifications can lead to protein denaturation, enzymatic inhibition, and disruption of cellular signaling pathways, contributing to the drug's overall cytotoxicity. The formation of these protein-platinum adducts is a critical factor in the drug's pharmacokinetics, the development of systemic toxicities such as nephrotoxicity and ototoxicity, and the emergence of cellular resistance to platinum-based therapy [NIH PMC4924455]. Understanding these modifications is essential for optimizing platinum-based chemotherapy and developing strategies to mitigate adverse effects.

Other names

Cisplatin-protein adductsPlatinated proteinsPlatinum-protein complexesCisplatin-protein conjugates

Cisplatin forms covalent adducts with cellular proteins, primarily through coordination with sulfur-containing amino acid residues (cysteine and methionine), leading to structural and functional alterations of the proteins.