DNA (calicheamicin-binding site)

The induction of DNA double-strand breaks by calicheamicin occurs when the antitumor antibiotic calicheamicin, often employed as a cytotoxic payload in ADCs, binds specifically in the minor groove of DNA. Following activation (often by chemical reduction within the cell), calicheamicin undergoes Bergman cyclization, forming a highly reactive diradical species that abstracts hydrogens from the DNA backbone, ultimately causing double-strand scission. This is a dominant mechanism for the cell-killing effect of calicheamicin-derived ADCs and underlies the efficacy (and toxicity) of these agents. \n\nNote: \nThis entry is not a canonical individual target (such as a protein or conventional receptor) but instead denotes a DNA structural motif (the minor groove) and a mechanism by which DNA integrity is compromised using an external agent (calicheamicin). As such, the entry is best treated as a descriptor of a mechanism, not a molecular drug target per standard pharmacological nomenclature.

Other names

DNA minor groove (calicheamicin binding site)DNA double-strand breakDSB site

DNA minor groove binding by calicheamicin triggers Bergman cyclization, generating diradicals that abstract hydrogens from the DNA deoxyribose, causing double-strand breaks\nThe double-strand breaks result in apoptosis of the targeted cell