Molecular design of sequence specific DNA alkylating agents.

Article Details

Citation

Minoshima M, Bando T, Shinohara K, Sugiyama H

Molecular design of sequence specific DNA alkylating agents.

Nucleic Acids Symp Ser (Oxf). 2009;(53):69-70. doi: 10.1093/nass/nrp035.

PubMed ID
19749264 [ View in PubMed
]
Abstract

Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
ChlorambucilDNANucleotideHumans
Unknown
Cross-linking/alkylation
Details