In:
ChemBioChem, Wiley, Vol. 15, No. 1 ( 2014-01-03), p. 68-79
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.
Type of Medium:
Online Resource
ISSN:
1439-4227
,
1439-7633
DOI:
10.1002/cbic.201300622
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2020469-3
SSG:
12