Pyrrolobenzodiazepines

Calicheamicins, Duocarymycins and PBD dimers are all different types of DNA-damaging agents that are functionally similar to anthracyclines in that they all target the minor groove of DNA. The DNA double helix forms two grooves which are present as a result of the geometric conformation of the two antiparallel strands. The minor groove is narrower and consists of fewer exposed base pairs in comparison with the major groove. Calicheamicins bind the minor grooves of tumour cell DNA where it forms reactive diradical species that ultimately cause cleavage of the DNA strands at various locations. Duocarmycins and PBD dimers take effect in similar ways with the former acting as a DNA minor groove alkylating agent and the latter as a minor groove cross-linker. As with any normal tissue, damage to the DNA of a cancer cell induces cell death via apoptosis.