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Related Experiment Video

Updated: Jun 21, 2026

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Published on: January 20, 2016

Large, sequence-dependent effects on DNA conformation by minor groove binding compounds.

Denise S Tevis¹, Arvind Kumar, Chad E Stephens

¹Department of Chemistry, Georgia State University, Atlanta, GA 30302, USA.

Nucleic Acids Research

|July 7, 2009

Summary

Antiparasitic heterocyclic dications surprisingly bend ATATA DNA sequences significantly, altering DNA topology. These findings reveal how drug structure influences DNA binding and conformational changes.

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Published on: November 1, 2012

Area of Science:

Biochemistry
Molecular Biology
Medicinal Chemistry

Background:

Kinetoplast DNA (kDNA) is a unique mitochondrial DNA found in trypanosomatids.
Antiparasitic drugs targeting kDNA topology are crucial for treating diseases like sleeping sickness.
Understanding drug-DNA interactions is key to developing novel therapeutic agents.

Purpose of the Study:

To investigate the topological changes induced by antiparasitic heterocyclic dications on DNA.
To elucidate the mechanism by which these compounds interact with and bend DNA sequences.

Main Methods:

Construction of DNA ligation ladders with phased A5 and ATATA sequences.
Complex formation between DNA models and three novel diamidine compounds (furan, thiophene, selenophene) and netropsin.
Analysis of DNA bending angles using gel electrophoresis.

Main Results:

A5 sequences showed expected DNA bending, while ATATA sequences exhibited minimal bending.
All tested diamidine compounds induced significant DNA bending in ATATA sequences, comparable to or exceeding A5 bending.
Compounds bent ATATA DNA into the minor groove, similar to their interaction with A5 tracts.

Conclusions:

Heterocyclic diamidines can induce substantial DNA bending in ATATA sequences, previously thought to be rigid.
The binding mechanism involves conformational changes, where wider ATATA grooves close upon drug interaction.
These findings provide insights into drug-induced DNA topology modulation for antiparasitic drug design.