Molecular recognition between ligands and nucleic acids: DNA binding characteristics of analogs of Hoechst 33258 designed to exhibit altered base and sequence recognition

The DNA binding characteristics of new analogues (2-8) of Hoechst 33258 (1), containing pyridine and benzoxazole units and designed for altered base specificity, were evaluated using UV, fluorescence, and circular dichroism studies. Like Hoechst 33258 the new analogues also bind through the minor gr...

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Bibliographic Details
Published in:Chemical research in toxicology 1991-11, Vol.4 (6), p.661-669
Main Authors: Rao, K. Ekambareswara, Lown, J. William
Format: Article
Language:English
Subjects:
Antineoplastic agents
Base Sequence
Biological and medical sciences
Bisbenzimidazole - metabolism
Circular Dichroism
DNA - metabolism
General aspects
Medical sciences
Nucleic Acid Conformation
Osmolar Concentration
Pharmacology. Drug treatments
Poly dA-dT - metabolism
Polydeoxyribonucleotides - metabolism
Structure-Activity Relationship
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Summary:The DNA binding characteristics of new analogues (2-8) of Hoechst 33258 (1), containing pyridine and benzoxazole units and designed for altered base specificity, were evaluated using UV, fluorescence, and circular dichroism studies. Like Hoechst 33258 the new analogues also bind through the minor groove of B-DNA in a nonintercalative fashion. The interaction of the compounds with poly(dA-dT) is salt independent. The studies with poly(dA-dT), ct DNA, and poly(dG-dC) indicated a decrease in the relative binding strength of the new analogues to DNAs compared with the parent molecule, Hoechst 33258. Compounds 5 and 7 showed acceptance of GC bases adjacent to AT base pairs. None of the compounds studied exhibited affinity for A-DNA, double-stranded RNA, or Z-DNA. Structure-DNA binding relationships of the new analogues compared with their parent molecule, Hoechst 33258, are discussed.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx00024a011