Binding of polybenzamides to DNA: studies by DNase I and chlorambucil interference footprinting and comparison with Hoechst 33258.
The DNA sequence-specific binding ability of polybenzamide minor groove binding ligands was investigated. These ligands were compared with the known minor groove binder Hoechst 33258, using both DNase I footprinting and chlorambucil interference footprinting. The monocationic derivative showed some sequence specific binding to A/T-rich sequences, as shown by DNase I footprinting, but results for the biscationic polybenzamide were inconclusive. A general non-specific inhibition of cleavage at high drug concentrations was observed, suggesting these compounds had a low DNA binding affinity compared to Hoechst 33258. Using a complementary technique, chlorambucil interference footprinting, the biscationic derivative displayed a clear preference for sites containing at least three consecutive adenines and in contrast with the monocationic analogue, a lesser affinity for mixed A/T sequences.
Turner
P R
PR
Auckland Cancer Society Research Centre, Faculty of Medicine and Health Science, University of Auckland, New Zealand.
Ferguson
L R
LR
Denny
W A
WA
D018906:Antineoplastic Agents, Alkylating / Q000378:metabolism*; D001549:Benzamides / Q000378:metabolism*; D001665:Binding Sites; D002699:Chlorambucil / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004347:Drug Interactions
D018906:Antineoplastic Agents, Alkylating; D001549:Benzamides; D002699:Chlorambucil; D004247:DNA; D003850:Deoxyribonuclease I