title: Structure-dependent binding of arylimidamides to the DNA minor groove.
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 Tm , 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.
authors: Department of Chemistry, Georgia State University, 50 Decatur St. SE., Atlanta, GA 30303 (USA).
authors: Yun
authors: Y
authors: Chai
authors: Manoj
authors: M
authors: Munde
authors: Arvind
authors: A
authors: Kumar
authors: Leah
authors: L
authors: Mickelson
authors: Sen
authors: S
authors: Lin
authors: Nancy H
authors: NH
authors: Campbell
authors: Moloy
authors: M
authors: Banerjee
authors: Senol
authors: S
authors: Akay
authors: Zongying
authors: Z
authors: Liu
authors: Abdelbasset A
authors: AA
authors: Farahat
authors: Raja
authors: R
authors: Nhili
authors: Sabine
authors: S
authors: Depauw
authors: Marie-Hélène
authors: MH
authors: David-Cordonnier
authors: Stephen
authors: S
authors: Neidle
authors: W David
authors: WD
authors: Wilson
authors: David W
authors: DW
authors: Boykin
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D007891:Leishmania / Q000378:metabolism; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance; D044366:Transition Temperature; D014349:Trypanosoma cruzi / Q000378:metabolism
chemical_list: D000577:Amides; D004247:DNA; D003850:Deoxyribonuclease I
keywords: DNA; X-ray crystallography; arylimidamides; minor-groove binders; molecular modeling