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Structure‐Dependent Binding of Arylimidamides to the DNA Minor Groove
Author(s) -
Chai Yun,
Munde Manoj,
Kumar Arvind,
Mickelson Leah,
Lin Sen,
Campbell Nancy H.,
Banerjee Moloy,
Akay Senol,
Liu Zongying,
Farahat Abdelbasset A.,
Nhili Raja,
Depauw Sabine,
DavidCordonnier MarieHélène,
Neidle Stephen,
Wilson W. David,
Boykin David W.
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300622
Subject(s) - circular dichroism , dna , chemistry , substituent , footprinting , minor groove , surface plasmon resonance , stereochemistry , fluorescence , binding site , crystallography , biophysics , biochemistry , biology , nanotechnology , materials science , base sequence , physics , quantum mechanics , nanoparticle
Abstract Heterocyclic diamidines are strong DNA minor‐groove binders and have excellent antiparasitic activity. To extend the biological activity of these compounds, a series of arylimidamides (AIAs) analogues, which have better uptake properties in Leishmania and Trypanosoma cruizi than diamidines, was prepared. The binding of the AIAs to DNA was investigated by T m , fluorescence displacement titration, circular dichroism, DNase I footprinting, biosensor surface plasmon resonance, X‐ray crystallography and molecular modeling. These compounds form 1:1 complexes with AT sequences in the DNA minor groove, and the binding strength varies with substituent size, charge and polarity. These substituent‐dependent structure and properties provide a SAR that can be used to estimate K values for binding to DNA in this series. The structural results and molecular modeling studies provide an explanation for the differences in binding affinities for AIAs.