Binding of polybenzamides to DNA: studies by DNase I and chlorambucil interference footprinting and comparison with Hoechst 33258

Citation
Pr. Turner et al., Binding of polybenzamides to DNA: studies by DNase I and chlorambucil interference footprinting and comparison with Hoechst 33258, ANTI-CAN DR, 13(8), 1998, pp. 941-954
Citations number
21
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ANTI-CANCER DRUG DESIGN
ISSN journal
02669536 → ACNP
Volume
13
Issue
8
Year of publication
1998
Pages
941 - 954
Database
ISI
SICI code
0266-9536(199812)13:8<941:BOPTDS>2.0.ZU;2-#
Abstract
The DNA sequence-specific binding ability of polybenzamide minor groove bin ding ligands was investigated. These ligands were compared with the known m inor groove binder Hoechst 33258, using both DNase I footprinting and chlor ambucil interference footprinting. The monocationic derivative showed some sequence specific binding to A/T-rich sequences, as shown by DNase I footpr inting, 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 compar ed to Hoechst 33258. Using a complementary technique, chlorambucil interfer ence footprinting, the biscationic derivative displayed a clear preference for sites containing at least three consecutive adenines and, in contrast w ith the monocationic analogue, a lesser affinity for mixed A/T sequences.