Evaluation of the DNA Alkylation Properties of a Chlorambucil?Conjugated Cyclic Pyrrole?Imidazole Polyamide

Hairpin pyrrole-imidazole polyamides (hPIPs) and their chlorambucil (Chb) conjugates (hPIP-Chbs) can alkylate DNA in a sequence-specific manner, have been studied as anticancer drugs. Here, we conjugated Chb to cyclic PIP (cPIP), which is known higher binding affinity than the corresponding hPIP, investigated alkylation properties of resulting cPIP-Chb using optimized capillary electrophoresis method conventional HPLC product analysis. conjugate 3 showed activity at its sites did hPIP-Chb 1 2. Subsequent analysis revealed that site 3, was identified by electrophoresis, reliable alkylates N3 position adenine do hPIP-Chbs. Moreover, cytotoxicity against LNCaP prostate cancer cells comparable These results suggest cPIP-Chbs could be novel alkylating