title: Investigation of the electrostatic and hydration properties of DNA minor groove-binding by a heterocyclic diamidine by osmotic pressure.
abstract: Previous investigations of sequence-specific DNA binding by model minor groove-binding compounds showed that the ligand/DNA complex was destabilized in the presence of compatible co-solutes. Inhibition was interpreted in terms of osmotic stress theory as the uptake of significant numbers of excess water molecules from bulk solvent upon complex formation. Here, we interrogated the AT-specific DNA complex formed with the symmetric heterocyclic diamidine DB1976 as a model for minor groove DNA recognition using both ionic (NaCl) and non-ionic cosolutes (ethylene glycol, glycine betaine, maltose, nicotinamide, urea). While the non-ionic cosolutes all destabilized the ligand/DNA complex, their quantitative effects were heterogeneous in a cosolute- and salt-dependent manner. Perturbation with NaCl in the absence of non-ionic cosolute showed that preferential hydration water was released upon formation of the DB1976/DNA complex. As salt probes counter-ion release from charged groups such as the DNA backbone, we propose that the preferential hydration uptake in DB1976/DNA binding observed in the presence of osmolytes reflects the exchange of preferentially bound cosolute with hydration water in the environs of the bound DNA, rather than a net uptake of hydration waters by the complex.
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: Noa
authors.initials: N
authors.lastname: Erlitzki
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: Suela
authors.initials: S
authors.lastname: Xhani
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Abdelbasset A
authors.initials: AA
authors.lastname: Farahat
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, United States. Electronic address: gpoon@gsu.edu.
authors.forename: Gregory M K
authors.initials: GMK
authors.lastname: Poon
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009997:Osmotic Pressure; D010419:Pentamidine / Q000737:chemistry* / Q000378:metabolism; D012965:Sodium Chloride / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D012965:Sodium Chloride; D010419:Pentamidine; D004247:DNA
keywords: Co-solute; Drug/DNA interactions; Heterocyclic dications; Molecular hydration; Osmotic pressure; Wyman linkages