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Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC Crosslinking of Small Molecules to Isolate Chromatin
Published on: January 20, 2016
High-affinity A/T-rich DNA binding with a dimeric bisbenzamidine
David Bouzada1, Ananya Paul2, Mateo I Sánchez1
1Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain.
None:
A bisbenzamidine DNA binding agent can be easily dimerized by alkylation of its terminal amidine groups to afford an extended minor groove binder with over 20-fold enhanced DNA affinity toward extended A/T-rich sites. Nuclear magnetic resonance experiments in combination with molecular dynamics simulation studies provide structural insight into the insertion of this compound in the DNA minor groove, and antimicrobial assays demonstrate that the increased affinity translates into higher antileishmanial activity.
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