期刊
BIOPHYSICAL CHEMISTRY
卷 231, 期 -, 页码 95-104出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bpc.2017.02.008
关键词
Osmotic pressure; Drug/DNA interactions; Co-solute; Heterocyclic dications; Molecular hydration; Wyman linkages
资金
- NSF [MCB 15451600]
- NIH [R21 HL129063]
- University Assistantship Program at Georgia State University
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1545160] Funding Source: National Science Foundation
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. (C) 2017 Elsevier B.V. All rights reserved.
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