Synthesis and DNA-Damaging Properties of Cisplatin-N-Mustard Conjugates

We report the synthesis of two novel cisplatin-N-mustard conjugates. In these compounds two potentially DNA-damaging molecules are combined and are separated by a spacer containing either one or four ethylene glycol units. We have shown that these conjugates are capable of forming novel clustered DNA adducts, thereby strongly increasing the lesion density in double-stranded DNA, which is thought to block DNA repair and translesion synthesis. Their ability to inhibit cell division was proven in an E. coli assay.