Microcalorimetry of interaction of dihydro-imidazo-phenanthridinium (DIP)-based compounds with duplex DNA

Guthrie, K.M., Parenty, A.D.C., Smith, L.V., Cronin, L. and Cooper, A. (2007) Microcalorimetry of interaction of dihydro-imidazo-phenanthridinium (DIP)-based compounds with duplex DNA. Biophysical Chemistry, 126(1-3), pp. 117-123. (doi: 10.1016/j.bpc.2006.05.006)

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Publisher's URL: http://dx.doi.org/10.1016/j.bpc.2006.05.006


Isothermal titration (ITC) and differential scanning calorimetry (DSC) have been used to screen the binding thermodynamics of a family of DNA intercalators based on the dihydro-imidazo-phenanthridinium (DIP) framework. All members of this DIP-based ligand family bind to both genomic (calf thymus and/or salmon testes) and a synthetic dodecamer d(CGCGAATTCGCG) duplex DNA with broadly similar affinities regardless of side chain size or functionality. Viscosity measurements confirm that binding satisfies standard criteria for intercalation. Binding is exothermic but with an additional favourable positive entropy contribution in most cases at 25 °C, although a significant negative heat capacity effect (ΔCp) means that both ΔH° and ΔS° decrease with increasing temperature. DIP-ligand binding to DNA also shows significant entropy–enthalpy compensation effects that are now almost standard in such situations, probably reflecting the conformational flexibility of macromolecular systems involving a multiplicity of weak non-covalent interactions. This ability to vary side chain functionality without compromising DNA binding suggests that the DIP framework should be a promising basis for more adventurous chemistry at the DNA level.

Item Type:Articles
Keywords:Isothermal titration calorimetry (ITC); Differential scanning calorimetry (DSC); Viscosity; Intercalation
Glasgow Author(s) Enlighten ID:Parenty, Mr Alexis and Cooper, Professor Alan and Cronin, Professor Lee
Authors: Guthrie, K.M., Parenty, A.D.C., Smith, L.V., Cronin, L., and Cooper, A.
Subjects:Q Science > QD Chemistry
College/School:College of Science and Engineering > School of Chemistry
University Centres > Glasgow Materials Research Initiative
Journal Name:Biophysical Chemistry
Publisher:Elsevier BV
ISSN (Online):1873-4200
Published Online:05 June 2006

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